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Review
Hypervalent Iodine Reagents in High Valent
Transition Metal Chemistry
Felipe Cesar Sousa e Silva, Anthony F. Tierno and Sarah E. Wengryniuk *
Department of Chemistry, Temple University, 1901 N. 13th St., Philadelphia, PA 19122, USA;
[email protected] (F.C.S.S.); [email protected] (A.F.T.)
* Correspondence: [email protected]; Tel.: +1-215-204-0360
Academic Editor: Margaret A. Brimble
Received: 29 March 2017; Accepted: 8 May 2017; Published: 12 May 2017
Abstract: Over the last 20 years, high valent metal complexes have evolved from mere curiosities
to being at the forefront of modern catalytic method development. This approach has enabled
transformations complimentary to those possible via traditional manifolds, most prominently
carbon-heteroatom bond formation. Key to the advancement of this chemistry has been the
identification of oxidants that are capable of accessing these high oxidation state complexes.
The oxidant has to be both powerful enough to achieve the desired oxidation as well as provide
heteroatom ligands for transfer to the metal center; these heteroatoms are often subsequently
transferred to the substrate via reductive elimination. Herein we will review the central role that
hypervalent iodine reagents have played in this aspect, providing an ideal balance of versatile
reactivity, heteroatom ligands, and mild reaction conditions. Furthermore, these reagents are
environmentally benign, non-toxic, and relatively inexpensive compared to other inorganic oxidants.
We will cover advancements in both catalysis and high valent complex isolation with a key focus
on the subtle effects that oxidant choice can have on reaction outcome, as well as limitations of
current reagents.
Keywords: hypervalent iodine; oxidation; oxidant; redox; high valent; high oxidation state; catalysis
1. Introduction
Over the last 20 years, high valent metal complexes have transitioned from mere curiosities
to being at the forefront of modern catalytic method development. This approach has enabled
transformations complimentary to those possible via traditional manifolds, most prominently
carbon-heteroatom bond formation. Key to the advancement of this chemistry has been the
identification of oxidants that are capable of accessing these high oxidation state complexes.
The oxidant has to be both powerful enough to achieve the desired oxidation as well as provide
heteroatom ligands for transfer to the metal center; these heteroatoms are often subsequently
transferred to the substrate via reductive elimination. The choice of heteroatom can be critical
depending on the application. For example, chloride ligands can aide in the stabilization and isolation
of high valent complexes whereas acetate ligands are often more successful in catalytic manifolds.
Hypervalent iodine reagents have seen wide application in this field as they are environmentally
benign, non-toxic, and relatively inexpensive compared to other inorganic oxidants. Furthermore, they
provide an excellent balance of versatile reactivity, heteroatom ligands, and mild reaction conditions.
We will cover advancements in the use of hypervalent iodine reagents for both catalysis and high
valent complex isolation with a key focus on the subtle effects that oxidant choice can have on reaction
outcome, as well as limitations of current reagents. Many of these areas have been covered in the
context of more broad reviews and in those cases the discussion will not be comprehensive but focus
on the key aspects and most relevant elements for this review. The discussion is organized broadly
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by the metal center being oxidized, including palladium, platinum, gold, nickel, copper, and finally
oxidized, including palladium, platinum, gold, nickel, copper, and finally isolated examples with
isolated examples with other transition metals. Below a summary graphic has been provided that
other transition metals. Below a summary graphic has been provided that includes oxidants common
includes oxidants common to high valent transition metal chemistry that will be discussed in this
to high valent transition metal chemistry that will be discussed in this review as well as common
review as well as common nomenclature and how they will be presented in the text (Figure 1).
nomenclature and how they will be presented in the text (Figure 1).
Hypervalent Iodine Reagents - Featured in blue throughout text
Other Oxidants Commonly Utilized
General reactivity towards transition metals
- 2-e – inner sphere oxidants (1-e – is possible but rare)
- Transfer of oxidant ligands to metal center (carbon or heteroatom)
- C–C or C–X reductive elimination pathways accessible
- Re-establishment of active catalysts
General reactivity towards transition metals
- 1e – or 2-e – inner sphere oxidants
- Generation of electrophilic metal center
- Can transfer functional groups to metal center (not always)
Advantages
- Powerful oxidants
- Broad ligand scope for transference to metal center
- Transfer of ligands resistant to reductive elimination
Advantages
- Powerful oxidants
- Inexpensive
- Non-toxic
- Environmentally benign
- Rapid synthesis
- Facile modulation of electronics and sterics
Disadvantage
- Expensive
- Harsh oxidantion conditions
- Minimal modulation of electronic/steric effects
Disadvantages
- Low atom economy
- Generate organic byproducts (ex- phenyl iodine, iodobenzoic acid)
- Limited by ligands available for transfer
Neutral, Acyclic λ3-Iodanes, Iodine(I) Reagents
O
O
I
R = Me; PhI(OAc) 2
phenyliodine(III)diacetate
R = CF3; PhI(OTFA) 2, PhI(OCOCF 3)2
phenyliodine(III) bis(trifluoroacetate)
R = Ph; PhI(O 2CPh) 2; PhI(OBz) 2
[bis-(benzoyloxy)iodo]benzene
R = tBu; PhI(O 2CtBu)2, PhI(OPiv) 2
phenyliodine(III)dipivalate
R
O
R
O
Cl
I
Me
Me
One-Electron Oxidants
OAc
I
OAc
OH
I
OTs
Cl
phenyliodine(III)dichloride
PhI(Cl) 2
Me
Hydroxo-phenyliodine(III)tosylate
PhI(OH)OTs, Koser's reagent
H
O
CuCl 2
t-butylhydrogenperoxide
tBuOOH, TBHP
O
O
N
Cl
O
N-Chlorosuccinimide
NCS
CH 3
IOAc
Iodine monoacetate
H 3C
Neutral, Cyclic, λ3-Iodanes
O
TIPS
Me
Me
Copper dichloride
N
Br
I
N
F
OTf
S
CF3
CH 3
1-Fluoro-2,4,6trimethylpyridinium triflate
NFTPT
O
S - (trifluoromethyl)dibenzothiophenium triflate
TDTT
N
1-[(triisopropylsilyl)ethynyl]-1,2benziodoxol-3(1H)-one;TIPS-EBX
(Poly)cationic, Acyclic λ3-Iodanes
R
I
N
2OTf
R = H [(Py) 2IPh]2OTf –
N,N dipyridinium phenyliodine(III) triflate
R = CN, [(4CNPy) 2IPh]2OTf –
N,N [4- cyano]dipyridinium phenyliodine(III) triflate
R = NMe 2, [(DMAP) 2IPh]2OTf –
N,N [4- dimethylamino]dipyridiniumphenyliodine(III) triflate
Iodonium salts
R
BF 4
I+
R
SiH3
N
1-Chloromethyl-4-fluoro-1,4diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate),
F-TEDA, SelectfluorR
PhO 2S
PhO 2S
N F
N-fluorobis(phenylsulfonyl)imide
NFSI
H 3C
I
Methyliodide,
MeI
PtCl 62Hexachloroplatinum(IV)
BF 4
R
Diaryliodonium tetrafluoroborate
[Ph 2I]BF 4
1,2 disilylbenzene
2KHSO5. KHSO 4.K 2SO4
OxoneR
I + C CR
SiH3
2BF4
F
N
O
Benzoquinone,
BQ
OTf
Cl
R
O
N-Bromosuccinimide
NBS
O
3,3 - Dimethyl-1-(trifluoromethyl)-1,2benziodoxole; Togni's reagent
Oxygen
Two-Electron Oxiants
[N-(phenylsulfonyl)imino]phenyliodinane
PhINTs
I
O2
O
I NTs
Iodomesitylene diacetate
MesI(OAc) 2
F 3C
O
O
Alkynylliodonium tetrafluoroborate
[PhICCR]BF 4
N
Cl
O
N-Chlorosuccinimide
NCS
Figure 1. Common oxidants utilized in high valent metal catalysis.
Figure 1. Common oxidants utilized in high valent metal catalysis.
O
N
Br
O
N-Bromosuccinimide
NBS
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2. Palladium
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2.1. Introduction
2. Palladium
Palladium has a long and storied history in transition metal catalysis, facilitating such iconic
Introduction
cross2.1.
coupling
reactions as the Heck, Suzuki-Miyara, Negishi, Buchwald-Hartwig, Sonagashira,
and others.
Its
ubiquity
stems
not only
fromin its
excellent
reactivity,
also from
a detailed
Palladium
has a long
and storied
history
transition
metal
catalysis, but
facilitating
such iconic
understanding
of reactions
its underlying
mechanisms
and Negishi,
predictable
reactivity, which
facilitates
cross coupling
as the Heck,
Suzuki-Miyara,
Buchwald-Hartwig,
Sonagashira,
andnovel
others.
Its ubiquity stems
not only
from palladium
its excellent reactivity,
but alsoon
from
detailed understanding
reaction
development.
For many
years,
catalysis relied
theaPd(0)/Pd(II)
redox couple,
of itswork
underlying
mechanisms
and shown
predictable
reactivity,
facilitates
novel
reaction state
however,
in the 21st
century has
the power
and which
promise
of the high
oxidation
development.
For
many
years,
palladium
catalysis
relied
on
the
Pd(0)/Pd(II)
redox
couple,
however,
Pd(II)/Pd(IV) manifold, as well as the potential role of Pd(III) species in catalysis (Scheme 1). This
work in the 21st century has shown the power and promise of the high oxidation state Pd(II)/Pd(IV)
chemistry
has enabled transformations previously inaccessible via traditional catalytic manifolds,
manifold, as well as the potential role of Pd(III) species in catalysis (Scheme 1). This chemistry has
most notably carbon-heteroatom bond forming reductive eliminations, the microscopic reverse of the
enabled transformations previously inaccessible via traditional catalytic manifolds, most notably
oxidative
addition pathways commonly encountered in low valent palladium catalysis. In this context,
carbon-heteroatom bond forming reductive eliminations, the microscopic reverse of the oxidative
hypervalent
reagents
haveencountered
emerged asinkey
players,
net two-electron
oxidations
addition iodine
pathways
commonly
low
valent facilitating
palladium catalysis.
In this context,
at thehypervalent
metal center
accompanied
transfer
heteroatom
most commonly
iodine
reagents haveby
emerged
as of
keytheir
players,
facilitatingligands,
net two-electron
oxidations acetate
at
or chloride.
Arguably
the rapid advancements
andheteroatom
synthetic applications
high valent
palladium
the metal
center accompanied
by transfer of their
ligands, mostof
commonly
acetate
or
chloride.
Arguably
rapid advancements
andobscure
synthetic
applications
of with
high other
valentmetals.
palladium
chemistry
have
spurredthe
investigations
into more
oxidation
states
As both
chemistry
have
spurred
investigations
into
more
obscure
oxidation
states
with
other
metals.
As both
synthetic applications and mechanistic details of this area have been comprehensively discussed
in
synthetic
applications
mechanistic
of this
area have
comprehensively
discussed
in
several
excellent
reviews and
in recent
years details
[1–8], this
section
will been
discuss
the key role that
hypervalent
several excellent reviews in recent years [1–8], this section will discuss the key role that hypervalent
iodine
reagents have played in its development, with special attention paid to recent reports as well
iodine reagents have played in its development, with special attention paid to recent reports as well
as limitations of current methods that could be addressed through continued exploration of novel
as limitations of current methods that could be addressed through continued exploration of novel
oxidants.
As the body of work in this area is extensive, this section will be organized based on the
oxidants. As the body of work in this area is extensive, this section will be organized based on the
type type
of bond
formation
being
targeted,
C–X,C–N,
C–N,and
and
C–C
bonds,
finally
studies
of bond
formation
being
targeted,namely
namely C–O,
C–O, C–X,
C–C
bonds,
andand
finally
studies
focusing
on
Pd(III)
species.
focusing on Pd(III) species.
Traditional: Pd(0)/Pd(II) Cross Coupling
Pd 0
Oxidative
Addition
R X
R Pd II X
Transmetallation
[M] R1
R Pd II R1
Suzuki, Heck, Negishi,
Buchwald-Hartwig,
Stille, Sonagashira, etc.
R R1
C–C Reductive Elimination
Last 20 years: Pd(II)/Pd(IV) Manifolds: C–H Functionalization, Alkene Difunctionalization, Allylic Oxidation
R Pd II X
PdX 2
[O]
X
X
R
Pd IV X
X
R
X
Pd III Pd III R
X
X
[O] = PhI(OR) 2, PhIX 2, [R 2I]X –, ArINTs,
[(Py) 2IPh] 2X–
NCS, NBS, NFSI, TTDT, others
C– X Reductive Elimination
or S N2-Displacement
R X
Scheme 1. Manifolds for palladium catalysis. Traditional methods via Pd(0)/Pd(II) and recent
Scheme 1. Manifolds for palladium catalysis. Traditional methods via Pd(0)/Pd(II) and recent advances
advances in Pd(II)/Pd(IV) catalysis.
in Pd(II)/Pd(IV) catalysis.
2.2. Palladium(IV)
2.2. Palladium(IV)
2.2.1. Introduction
2.2.1. Introduction
Canty reported the first X-ray structure of an alkyl Pd(IV) organometallic complex in 1986,
Canty
reported
the first
X-rayof structure
of to
ana alkyl
Pd(IV)
organometallic
complex
in 1986,
formed via
the oxidative
addition
iodomethane
dimethyl
(bpy)Pd(II)
complex (1, Scheme
2) [9].
formed
via the
oxidative
of iodomethane
to Pd(IV)
a dimethyl
(bpy)Pd(II)
(1, oxidative
Scheme 2) [9].
Canty’s
work
revealedaddition
the octahedral
geometry of
species
1, as well complex
as the clean
addition/reductive
reactivity
and stability
of thesespecies
complexes,
Canty’s
work revealedelimination
the octahedral
geometry
of Pd(IV)
1, aswhich
well he
ascomments
the cleancould
oxidative
“suggest
that
development
of
a
rich
organometallic
chemistry
of
palladium(IV)
may
be
possible”.
addition/reductive elimination reactivity and stability of these complexes, which he comments could
This that
report
laid the foundation
the rich chemistry,
mechanistic
and structuralmay
understanding
of This
“suggest
development
of a richfororganometallic
chemistry
of palladium(IV)
be possible”.
this high oxidation state redox couple that has emerged over the last 20 years.
report laid the foundation for the rich chemistry, mechanistic and structural understanding of this high
oxidation state redox couple that has emerged over the last 20 years.
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Molecules 2017, 22, 780
N
N
Pd II
Me
MeI
Me Oxidation
1
N
N
Me
Pd IV
I 2
Me
- (CH3)2
Me C–C Reductive
Elimination
N
N
Pd II
4 of 54
Me
I
Scheme
2. Canty’s
reportin
resulting
in X-ray
the first
X-ray crystallographic
characterization
a Pd(IV)alkyl species.
Scheme 2. Canty’s
report
resulting
the first
crystallographic
characterization
of of
a Pd(IV)
alkyl species.
Pd(II)/Pd(IV) chemistry has become as a powerful synthetic manifold to facilitate transformations
Pd(II)/Pd(IV) chemistry has become as a powerful synthetic manifold to facilitate transformations
not accessible
via traditional Pd(0)/Pd(II) catalysis (Scheme 1). This field has been pioneered by the
not accessible via traditional Pd(0)/Pd(II) catalysis (Scheme 1). This field has been pioneered by
Sanford the
group
in group
the area
C–H
acetoxylation
halogenation.
There
been several
Sanford
in theof
area
of C–H
acetoxylation and
and halogenation.
There
have have
been several
comprehensive
reviews
written
topic
in recent
years
readerthere
is directed
comprehensive
reviews
writtenon
on this
this topic
in recent
years and
the and
readerthe
is directed
for detailedthere for
mechanistic
discussion
and
an
exhaustive
report
of
applications
[1,4,5].
Building
from
this work,
detailed mechanistic discussion and an exhaustive report of applications [1,4,5]. Building
from this
Pd(IV) chemistry has been applied to the formation of a diverse array of C–N, C–O, C–X, and C–C
work, Pd(IV) chemistry has been applied to the formation of a diverse array of C–N, C–O, C–X, and
bond forming reactions.
C–C bond forming reactions.
2.2.2. Carbon–Oxygen Bond Formation
2.2.2. Carbon–Oxygen
Bond
Formation
There has been
extensive
work in the area of C–O bond formation via Pd(II)/Pd(IV) catalysis
with hypervalent iodine reagents. This application is particularly well suited as the most common
There
has been extensive work in the area of C–O bond formation via Pd(II)/Pd(IV) catalysis
hypervalent iodine oxidants, of the type PhI(OR)2 , transfer carboxylate ligands to the metal center that
with hypervalent
iodine reagents. This application is particularly well suited as the most common
are then engaged in subsequent C–O bond forming reductive elimination. These carboxylate ligands
hypervalent
iodine
oxidants,
of the
type and
PhI(OR)
2, transfer
carboxylate
ligands
to the
metal center
are also
highly
tunable, both
sterically
electronically,
allowing
for control
of complex
stability,
pathway and
selectivity. Approaches
haveforming
expandedreductive
to include C–H
functionalization,
that are reaction
then engaged
in subsequent
C–O bond
elimination.
Theseallylic
carboxylate
oxidation,
as well as
alkene difunctionalization.
ligands are
also highly
tunable,
both sterically and electronically, allowing for control of complex
stability, 2.2.2.1.
reaction
pathway
and selectivity. Approaches have expanded to include C–H functionalization,
C–H
Functionalization
allylic oxidation, as well as alkene difunctionalization.
The first report of Pd-catalyzed C–H acetoxylation using a hypervalent iodine oxidant was by
Crabtree, who achieved the acetoxylation of benzene using Pd(OAc)2 with PhI(OAc)2 as the external
2.2.2.1. C–H
Functionalization
oxidant
and –OAc source (Scheme 3) [10]. This built upon the work of Stock et al., which employed
dichromate to perform an analogous transformation [11], however PhI(OAc)2 offered much higher
The first report of Pd-catalyzed C–H acetoxylation using a hypervalent iodine oxidant was by
selectivity and did not perform further product oxidations. In what has become a standard mechanistic
Crabtree,proposal,
who achieved
acetoxylation
of benzene
using Pd(OAc)
2 with PhI(OAc)2 as the external
Crabtree the
proposed
acetyl assisted
C–H activation
at Pd(II) (intermediate
3) would give
oxidant and
–OAc
source
(Scheme
3)
[10].
This
built
upon
the
work
of
Stock
et
al.,
employed
intermediate 4, which can then be diverted down one of two pathways. Along the desiredwhich
pathway
(PathtoB)perform
5 is then oxidized
by PhI(OAc)
with introduction
of two
acetyl groups.
dichromate
an analogous
transformation
[11],5 however
PhI(OAc)
2 offered
much higher
2 to Pd(IV) species
Subsequent
reductive
elimination
gives
rise
to
acetoxylated
product
and
regeneration
of
the
Pd(OAc)
.
selectivity and did not perform further product oxidations. In what has become a 2standard
Importantly, Crabtree noted that competitive formation of biphenyl (via Path A) is minimized with
mechanistic
proposal, Crabtree proposed acetyl assisted C–H activation at Pd(II) (intermediate 3)
PhI(OAc)2 , indicating that oxidation to Pd(IV) in this system is significantly faster than a second C–H
would give
intermediate
4, which
canalso
then
be diverted
one
two pathways.
Along
the desired
activation
step to give
6. It was
found
that in thedown
absence
of of
oxidant,
biphenyl was
the only
pathwayobservable
(Path B) 5product,
is thenthus
oxidized
bythat
PhI(OAc)
2 to Pd(IV)4species
5 with introduction
of two acetyl
indicating
Pd(II) intermediate
will not undergo
direct C–X reductive
elimination, and
emphasizing
the significance
of rise
Pd(IV)
in facilitating
such
transformations.
groups. Subsequent
reductive
elimination
gives
to pathways
acetoxylated
product
and
regeneration of the
this system displayed
moderate
activity formation
and requiredof
solvent
quantities
the
Pd(OAc)While
2. Importantly,
Crabtreeonly
noted
thatcatalytic
competitive
biphenyl
(viaof Path
A) is
arene, it laid the foundation for the development of directed C–H acetoxylation, which has relied on
minimized with PhI(OAc)2, indicating that oxidation to 2Pd(IV) in this system
is significantly faster
hypervalent iodine oxidants to efficiently acetoxylate C(sp )–H as well as C(sp3 )–H bonds.
than a second C–H activation step to give 6. It was also found that in the absence of oxidant, biphenyl
was the only observable product, thus indicating that Pd(II) intermediate 4 will not undergo direct
C–X reductive elimination, and emphasizing the significance of Pd(IV) pathways in facilitating such
transformations. While this system displayed only moderate catalytic activity and required solvent
quantities of the arene, it laid the foundation for the development of directed C–H acetoxylation,
which has relied on hypervalent iodine oxidants to efficiently acetoxylate C(sp2)–H as well as C(sp3)–
H bonds.
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+ metallic palladium
Molecules 2017, 22, 780
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Pd II
+ metallic palladium
C–C Reductive Elimination
6
Pd II
PhI(OAc) 2
Path A6 Ph–H
minor
C–C Reductive Elimination
PhI(OAc) 2
H
H
Pd(OAc) 2
H
O
Path A Ph–H
Pd II(OAc)
minor
Pd O
H
O
O
O 3
Pd O
AssistedOC-H O
Activation
3
Pd(OAc) 2
- AcOH
- AcOH
4
Pd II(OAc)
Path B
major
PhI(OAc) 2
4
Path B PhI(OAc)
2
major OAc
Assisted C-H Activation
C–X Reductive Elimination
PdIV OAc
OAc
OAc
5
PdIV OAc
OAc
OAc
C–X Reductive
Elimination
OAc
5
Scheme 3. Pd(II)/Pd(IV) catalyzed acetoxylation of benzene with use of PhI(OAc)
2 as external oxidant.
Scheme 3. Pd(II)/Pd(IV) catalyzed acetoxylation of benzene with use of PhI(OAc)2 as external oxidant.
The
Sanford
group’s contributions
to this area
beganwith
in 2004
their2 as
seminal
on the
Scheme
3. Pd(II)/Pd(IV)
catalyzed acetoxylation
of benzene
use ofwith
PhI(OAc)
externalreport
oxidant.
The
Sanford
group’s contributions
to this area
began
in 2004
with their
seminal
report
on the
directed
C–H acetoxylation
of 2-phenylpyridine
using
Pd(OAc)
2/PhI(OAc)
2 (Scheme
4a) [12].
Since
2)–H
The
Sanford
contributions
thisinclude
area
began
in 2004
with
their
seminal
report
on
the
then,C–H
they
have group’s
extended
this methodto to
aPd(OAc)
range
of
directing
groups
for
C(sp
directed
acetoxylation
of
2-phenylpyridine
using
/PhI(OAc)
(Scheme
4a)
[12].
Since
2
2
2
directed
C–H
acetoxylation
of
2-phenylpyridine
using
Pd(OAc)
2/PhI(OAc)
2 (Scheme
4a)
[12].
Since
acetoxylation
and
a
brief
overview
is
included
in
Scheme
4b
[13].
While
other
oxidants
including
then, they have extended this method to include a range of directing groups for C(sp )–H acetoxylation
then, they
have
extended
this used
to include
a range
of 2 directing
groups
C(sp2)–H
2 and
Oxone
have been
in this
PhI(OAc)
is by far including
the
most for
common
[2]. and
and aMn(OAc)
brief overview
is included
in method
Scheme
4bchemistry,
[13]. While
other
oxidants
Mn(OAc)
2
acetoxylation
and a brief overview
is included
Schemeof4bthis
[13].
While other
oxidants
Sanford
also demonstrated
a polymer
supportedinvariant
chemistry,
which
allows including
for facile
Oxone have been used in this chemistry, PhI(OAc)2 is by far the most common [2]. Sanford also
Mn(OAc)of
2 and
Oxone have iodine
been used
in this
chemistry,
2 is by far the
most common
[2].
recycling
the hypervalent
reagent,
addressing
the PhI(OAc)
issue of iodobenzene
byproducts
produced
demonstrated
a polymer supported
variant
of this chemistry, which allows for facile recycling of
Sanford
also demonstrated
a polymer
supported variant of this chemistry, which allows for facile
in
these transformations
(Scheme
4c) [14].
the hypervalent
iodine
reagent,
addressing
the issue of
byproducts
produced
in these
recycling of the
hypervalent
iodine
reagent, addressing
theiodobenzene
issue of iodobenzene
byproducts
produced
a. (Scheme 4c)
b.
transformations
[14]. 4c) [14].
in these transformations
(Scheme
R
Directed C(sp 2 )–H acetoxylation
Pd(OAc) 2,
PhI(OAc) 2
N
a.
N
MeCN,
1002, °C
Pd(OAc)
R
PhI(OAc) 2
N
MeCN, 100 °C
R
N
Pd II
N
Pd II
c.
L
[O]
L
c.
N
N
AcO
I
I
N
Ph
N
N 2 )–H acetoxylation
Directed C(sp
N
R
N
OAc
N
Ph
N
R
R
[O]
AcO
OAc
OAc
L
L
b.
OAc
OAc
n
n
OAc
N
N
OAc Me
NOAc
OAc
N
L
PdIV
OAcL
N OAc
L
PdIV
L
OAc
R
O
OAc
N
R
O
OAc
R
N
N
Pd(OAc) 2
AcOH, 100 °C
Pd(OAc) 2
N
OAc
N
AcOH, 100 °C
1. Precipitate with CH3OH
OAc
2. Regenerate with AcO2H
OAc OMe
N
OAc Me
OMe
N
R
AcO
I
AcO
I
n
n
1. Precipitate with CH3OH
Scheme 4. (a) First report on the directed C(sp2)–H acetoxylation of 2-phenylpyridine with
2. Regenerate with AcO2H
Pd(OAc)2/PhI(OAc)2; (b) General scope of directing groups used for C(sp2)–H acetoxylation;
2)–H acetoxylation of 2-phenylpyridine with
Scheme
4. (a)
First
report
thedirected
directed
C(sp
allows
for facile
oxidant
(c)
Polymer-supported
λ3-iodane
2 )–Hrecycling.
Scheme
4. (a)
First
report
ononthe
C(sp
acetoxylation of 2-phenylpyridine with
acetoxylation;
Pd(OAc)2/PhI(OAc)2; (b) General scope of directing groups used for C(sp2)–H
Pd(OAc)2 /PhI(OAc)2 ; (b) General scope of directing groups
used for C(sp2 )–H acetoxylation;
3-iodane
The
acetoxylation of
benzylic
unactivated
C(sp3)–H bonds can also be accomplished
allowsand
for facile
oxidant recycling.
(c) Polymer-supported
3 λboth
(c) Polymer-supported λ -iodane allows for facile oxidant recycling.
with Pd(OAc)2 and PhI(OAc)2 (Scheme 5) [12,15,16]. In these reactions, sterics plays a large role in
The acetoxylation of both benzylic and unactivated C(sp3)–H bonds can also be accomplished
3 )–H bonds
with
Pd(OAc)2 and PhI(OAc)
2 (Schemeand
5) [12,15,16].
In these
sterics
large
role in
The acetoxylation
of both benzylic
unactivated
C(spreactions,
canplays
alsoabe
accomplished
with Pd(OAc)2 and PhI(OAc)2 (Scheme 5) [12,15,16]. In these reactions, sterics plays a large role in
Molecules 2017, 22, 780
6 of 54
Molecules 2017, 22, 780
6 of 54
Moleculesregioselectivity,
2017, 22, 780
6 of
54
dictating
with
thethe
lessless
sterically
hindered
C–HC–H
bond
undergoing
C–HC–H
activation.
While
dictating
regioselectivity,
with
sterically
hindered
bond
undergoing
activation.
3
3)–Hoften
theWhile
C(sp the
)–H C(sp
variant
performs
efficiently
PhI(OAc)
the oxidant,
combinations
variant
often most
performs
most with
efficiently
with2 as
PhI(OAc)
2 as the
oxidant,
dictating regioselectivity, with the less sterically hindered C–H bond undergoing C–H activation.
of combinations
Oxone/Mn(OAc)
and peroxide
oxidants
have
also been
used
of 3Oxone/Mn(OAc)
2, molecular
oxygen, and
peroxide
oxidants
have
alsoeffectively
been used[2].
2 , molecular oxygen,
While the C(sp )–H variant often performs most efficiently with PhI(OAc)2 as the oxidant,
effectively
[2]. Another
interesting
examplereagent
used iodine(I)
reagent
IOAc,
which was
generated
in situ
Another
interesting
example
used iodine(I)
IOAc, which
was
generated
in situ
from PhI(OAc)
combinations of Oxone/Mn(OAc)2, molecular oxygen, and peroxide oxidants have also been used 2
from
PhI(OAc)22 and
I2; was
PhI(OAc)
2 alonein
was
ineffective
and
I2 ; PhI(OAc)
alone
ineffective
this
case [17].in this case [17].
effectively [2]. Another interesting example used iodine(I) reagent IOAc, which was generated in situ
from PhI(OAc)2 and
I2; PhI(OAc)
2 alone was ineffective in this case [17].
a. Benzylic
C–H acetoxylation
Pd(OAc) 2,
X C–H acetoxylation
a. Benzylic
PhI(OAc) 2
R
Pd(OAc) 2,
AcOH/Ac2O, 100
°C
X
N
PhI(OAc) 2
R
H
AcOH/Ac2O, 100 °C
N
b. Unactivated C(sp 3 )-H acetoxylation
H
MeO
Pd(OAc) 2,
b. Unactivated
C(sp 3 )-H acetoxylation
N
PhI(OAc) 2
MeO
Pd(OAc) 2,
R
H AcOH/Ac
N
2O, 100 °C
PhI(OAc) 2
R1
R
H
X
R
X
N
OAc
N
R
OAc
MeO
MeO
R
R
N
N
OAc
R1
OAc
R = Me, R 1= Et
PhI(OAc) 2 75%
1 45%
Me,
Et
KR
2S=2O
8 R =
PhI(OAc) 2 75%
45%
K 2S2O8
AcOH/Ac2O, 100 °C
Scheme 5. (a) Directed acetoxylation
of benzylic C(sp3)–H
(b) Directed acetoxylation of
1
R1 bonds;
Scheme 5. (a) Directed Racetoxylation of benzylic C(sp3 )–H
bonds; (b) Directed acetoxylation of
3)–H bonds.
unactivated C(sp
3 )–H bonds.
unactivated
Scheme 5.C(sp
(a) Directed
acetoxylation of benzylic C(sp3)–H bonds; (b) Directed acetoxylation of
unactivated C(sp )–H bonds.
The
Sanford group has conducted extensive mechanistic studies on these processes, and the
The
Sanford
has
conducted
extensive
mechanistic
studies
on these
processes,
reader is
directedgroup
to some
selected
full reports
for detailed
discussion
[2,18–20].
Their
work hasand
beenthe
The
Sanford
group
has
conducted
extensive
mechanistic
studies
on
these
processes,
and
the
reader
is directed
to some
selected
full reports
discussion
Their
accompanied
by that
of Ritter
and others,
with afor
keydetailed
point being
whether[2,18–20].
Pd(IV) species
orwork
Pd(III)has
reader
is
directed
to
some
selected
full
reports
for
detailed
discussion
[2,18–20].
Their
work
has
been
been
accompanied
by that
of Ritter
others,
with athe
keypossibility
point being
whether
Pd(IV) species
dimers
are the active
catalysts.
Keyand
reports
detailing
of Pd(III)
intermediates
are or
accompanied
bythe
thatactive
of Ritter
and others,
with a detailing
key pointthe
being
whetherof
Pd(IV)
species
or Pd(III)are
Pd(III)
dimers
are
catalysts.
Key
reports
possibility
Pd(III)
intermediates
discussed in more detail in Section 1.3. Sanford’s seminal report in this area outlines some of the key
dimers are the active catalysts. Key reports detailing the possibility of Pd(III) intermediates are
discussed
morethe
detail
in Section
Sanford’s
seminal
report
in this
outlines
some
of the key
features in
of both
ligand
scaffolds2.3.
and
hypervalent
iodine
oxidants
thatarea
allow
for study
of reactive
discussed in more detail in Section 1.3. Sanford’s seminal report in this area outlines some of the key
features
both the ligand
scaffolds
and hypervalent
iodine
oxidants
thatTwo
allow
forcyclometallated
study of reactive
Pd(IV)of
intermediates
as well
as mechanistic
elucidation
(Scheme
6) [19].
rigid
features of both the ligand scaffolds and hypervalent iodine oxidants that allow for study of reactive
2-phenylpyridine
ligands
incorporated
to lend stability
complexes,
and
Pd(IV)
intermediates
as wellwere
as mechanistic
elucidation
(Schemeto6) the
[19].resultant
Two rigid
cyclometallated
Pd(IV) intermediates as well as mechanistic elucidation (Scheme 6) [19]. Two rigid cyclometallated
suppress competing
ligand
and side
reactions
upon
oxidation.
Additionally,
the acetate
2-phenylpyridine
ligands
wereexchange
incorporated
to lend
stability
to the
resultant
complexes, and
suppress
2-phenylpyridine ligands were incorporated to lend stability to the resultant complexes, and
ligands ofligand
PhI(OAc)
2 were exchanged
for aryl carboxylates
that could
be readily derivatized
thus of
competing
exchange
and side reactions
upon oxidation.
Additionally,
the acetateand
ligands
suppress competing ligand exchange and side reactions upon oxidation. Additionally, the acetate
used
as
facile
handles
to
control
the
electronic
parameters
at
the
metal
center.
The
Pd(IV)
complex
PhI(OAc)
exchanged
for aryl carboxylates that could be readily derivatized and thus (7)
used
ligands 2ofwere
PhI(OAc)
2 were exchanged for aryl carboxylates that could be readily derivatized and thus
obtained
upon
oxidation
with
PhI(CO2p–XAr)
2 where X=NO2 was able to characterized by X-ray
as used
facileashandles
to
control
the
electronic
parameters
at
the
metal
center.
The
Pd(IV)
complex
facile handles to control the electronic parameters at the metal center. The Pd(IV) complex (7) (7)
crystallography,
revealing cis addition
ofp–XAr)
the two carboxylates
ligands.
Subsequent
Hammett analysis
obtained
upon
oxidation
= NO
able
characterized
X-ray
2 2p–XAr)22 where
2 was
obtained upon
oxidationwith
withPhI(CO
PhI(CO
where X
X=NO
2 was
able
toto
characterized
byby
X-ray
revealed
a
clear
correlation
between
carboxylate
electronics
and
the
rate
of
reductive
elimination,
crystallography,
revealing
ciscisaddition
ligands.Subsequent
Subsequent
Hammett
analysis
crystallography,
revealing
additionof
ofthe
the two
two carboxylates
carboxylates ligands.
Hammett
analysis
indicating that the carboxylate acted in as a nucleophile in reductive elimination.
revealed
a
clear
correlation
between
carboxylate
electronics
and
the
rate
of
reductive
elimination,
revealed a clear correlation between carboxylate electronics and the rate of reductive elimination,
indicating
that
the
reductiveelimination.
elimination.
indicating
that
thecarboxylate
carboxylateacted
actedin
inas
asaa nucleophile
nucleophile in reductive
3
N
Pd II
N
I
O
O22C(p-XC
C(p-XC66H
H55))
R
I
X = H, OMe,OMe,
OPh,
F,
Cl,
Br,
2C(p-XC 6H 5)
R
Ac, CF3, CN, NO 2
R
X = H, OMe, Me, OPh, F, Cl, Br,
Hammett analysis shows correlation
between
carboxylate ligand
Ac, CF
3, CN, NO 2
electronics and rate of reductive elimination
N
Pd II
N
R
N
O 2C(p-XC 6H 5)
Hammett analysis shows correlation between carboxylate ligand
electronics and rate of reductive elimination
Pd IV
N
O 2C(p-XC 6H 5)
IV
O
Pd
2C(p-XC 6H 5)
N7
O 2C(p-XC 6H 5)
O 2C(p-XC
C-O 6H 5)
7
Reductive
Elimination
C-O
N
Reductive
Elimination
N
(C 6H 5 p-X)CO 2
N
Scheme 6. Seminal mechanistic investigation into Pd(IV)-mediated
C–H
acetoxylation.
(C 6H 5 p-X)CO
2
6. Seminal mechanistic investigation into
Pd(IV)-mediated C–H acetoxylation.
2)–H
The Scheme
YuScheme
group
reportedmechanistic
an intramolecular
C(spinto
acetoxylation that
also be rendered
6. Seminal
investigation
Pd(IV)-mediated
C–Hcould
acetoxylation.
asymmetric using a Boc-Ile-OH chiral ligand (Scheme 27) [21]. This report was the first enantioselective
The Yu group reported an intramolecular C(sp2)–H acetoxylation that could also be rendered
application
of Pd(II)/Pd(IV)
and gave high
yields
enantioselectivities
of benzofuranones.
The Yu group
reported catalysis
an intramolecular
C(sp
)–Hand
acetoxylation
that could
also be rendered
asymmetric using a Boc-Ile-OH chiral ligand (Scheme 7) [21]. This report was the first enantioselective
asymmetric
using
a
Boc-Ile-OH
chiral
ligand
(Scheme
7)
[21].
This
report
was
the
first
enantioselective
application of Pd(II)/Pd(IV) catalysis and gave high yields and enantioselectivities of benzofuranones.
application of Pd(II)/Pd(IV) catalysis and gave high yields and enantioselectivities of benzofuranones.
Molecules 2017, 22, 780
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7 of 54
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Molecules 2017, 22, 780
7 of 54
Ar
Pd(OAc) 2,
R
Molecules 2017, 22, 780
7 of 54
O
Boc-Ile-OH
Ar
Pd(OAc) 2,
Ar R
1
1
O
R
R
R
Boc-Ile-OH
PhI(OAc)
,
OHO
ArO
Pd(OAc) 22,
Ar R
RO
R1
R1
KOAc,
tBuOH
O
Boc-Ile-OH
PhI(OAc)
,
up
to
96%
ee
OH
2
O
O
R1
R1
KOAc,
tBuOH
PhI(OAc)
OH
2,
up tousing
96%
ee
22)–H acetoxylation
O
Scheme
7.
Enantioselective
intramolecular
C(sp
chiral
amino
acid
ligand.
Scheme 7. Enantioselective intramolecular KOAc,
C(sp )–H
acetoxylation using chiral
amino
acid
ligand.
tBuOH
up to 96% ee
2
Scheme 7. Enantioselective intramolecular C(sp )–H acetoxylation using chiral amino acid ligand.
Ar
R
Sanford demonstrated an impressive example
of non-directed C(sp2)–H
acetoxylation through
2 )–H
Scheme
7. Enantioselective
intramolecular
C(sp2)–H
acetoxylation
using
chiral
amino
acid ligand.through
Sanford
demonstrated
an
impressive
example
of
non-directed
C(sp
acetoxylation
the addition
of
pyridine
to
enhance
catalytic
activity
of
the
palladium
catalyst
(Scheme
8) [22].
In this
2
Sanford demonstrated an impressive example of non-directed C(sp )–H acetoxylation
through
thesystem,
addition
of
pyridine
to
enhance
catalytic
activity
of
the
palladium
catalyst
(Scheme
8) [22].
In this
the
ratio
of
[Pd]/pyridine
proved
critical
as
well
as
the
selection
of
hypervalent
iodine
2)–H (Scheme
the addition
pyridine to enhance
catalyticexample
activity of
of non-directed
the palladiumC(sp
catalyst
8) [22].
In this
Sanfordofdemonstrated
an impressive
acetoxylation
through
system,
theSwitching
ratio of to
[Pd]/pyridine
proved
criticalMesI(OAc)
as well as
the PhI(OAc)
selection2 of
hypervalent
iodine
oxidant.
thetomore
sterically
hindered
improved
bothiodine
yield
system,
the ratio
of [Pd]/pyridine
proved
critical
as2 from
the selection
hypervalent
the addition
of pyridine
enhance
catalytic
activityas
of well
the palladium
catalystof
(Scheme
8) [22].
In
this
oxidant.
Switching
to
the
more
sterically
hindered
MesI(OAc)
from
PhI(OAc)
improved
both
yield
2
2
and
regioselectivity.
oxidant.
Switching
to [Pd]/pyridine
the more sterically
hindered
PhI(OAc)of
2 improved
bothiodine
yield
system,
the ratio of
proved
criticalMesI(OAc)
as well as2 from
the selection
hypervalent
and
regioselectivity.
and
regioselectivity.
oxidant.
Switching to the
2 from PhI(OAc)2 improved both yield
Cl more sterically hindered MesI(OAc)
Cl
Cl
and regioselectivity.
2mol%
[Pd]
Cl
Cl
OAc
Cl
Cl
Cl
Cl
Cl
ArI(OAc)
2, AcOH/Ac
2mol%
[Pd] 2O
100 °C
ArI(OAc)
2mol%
[Pd] 2O
2, AcOH/Ac
100 °C
ArI(OAc)2, AcOH/Ac2O
[O]
[Pd]
100 °C
PhI(OAc)
Pd(OAc)
[O] 2
[Pd] 2
Cl
Cl
Cl
MesI(OAc) 2
PhI(OAc)
[O] 2
PhI(OAc) 2
MesI(OAc)
PhI(OAc) 22
MesI(OAc)
PhI(OAc) 222
MesI(OAc)
Pd(OAc) 2
Pd(OAc)
[Pd] 2
Pd(OAc)
2 /pyr (1:0.9)
Pd(OAc)
Pd(OAc)22
Pd(OAc)
(1:0.9)
2 /pyr
Pd(OAc)
Pd(OAc)
2 /pyr (1:0.9)
2
MesI(OAc)
PhI(OAc) 22
Pd(OAc)
Pd(OAc)22/pyr
/pyr(1:0.9)
(1:0.9)
Cl
+
Cl
α
OAc
OAc
α
Yield
α 8
Yield
8
8
Yield
59
88
64
59
8
64
59
+
+
Cl
Cl
α : β
Cl
β
β
OAc
OAc
OAc
β
41
α :: 59
β
37 : 63
41α :: 59
β
29
:: 71
37
63
41 : 59
11
: 89
29
37 :: 71
63
11
29 :: 89
71
Scheme 8. Non-directed arene C–H acetoxylation. Effect of both catalyst and hypervalent iodine
MesI(OAc) 2
Pd(OAc) 2 /pyr (1:0.9)
64
11 : 89
oxidant
on reactivity.
Scheme
Non-directedarene
areneC–H
C–H acetoxylation.
acetoxylation. Effect
iodine
Scheme
8. 8.Non-directed
Effectofofboth
bothcatalyst
catalystand
andhypervalent
hypervalent
iodine
oxidant
oxidant
onon
reactivity.
Scheme
8. reactivity.
Non-directed arene C–H acetoxylation. Effect of both catalyst and hypervalent iodine
Chen reported C(sp3)–H and C(sp2)–H alkoxylation using a picolinamide directing group
oxidant on reactivity.
(Scheme
9) [23].
The reaction
is proposed
proceed
via displacement
of acetate ligands
by alkoxides
2)–H
Chen
reported
C(sp3)–H
and C(sp2to
alkoxylation
using a picolinamide
directing
group
Chen
reported
C(sp3(8).
)–H
and
C(sp
)–H
alkoxylation
using
a
picolinamide
directing
group
at
a
Pd(IV)
intermediate
The
authors
rule
out
an
alternative
S
N
2-displacement
of
Pd(IV)
by group
ROH
2)–H
(Scheme
9) [23].
The reaction
is proposed
proceed
via displacement
acetate ligands
by alkoxides
Chen
reported
C(sp3)–H
and C(spto
alkoxylation
using a of
picolinamide
directing
(Scheme
9)
[23].
The
reaction
is
proposed
to
proceed
via
displacement
of
acetate
ligands
by
alkoxides
since
t-BuOH
also
participates
to
give
C–OR
bond
formation.
This
reactivity
is
divergent
from
their
at
a Pd(IV)
(8). The
authors rule
out an alternative
SN2-displacement
of Pd(IV)
by ROH
(Scheme
9) intermediate
[23]. The reaction
is proposed
to proceed
via displacement
of acetate ligands
by alkoxides
at previous
asince
Pd(IV)
intermediate
(8).amination
Theto
authors
rule
out
anformation.
alternative
SN reactivity
2-displacement
of selective
Pd(IV)
by
ROH
reports
on
C–H
using
this
same
system,
where
8
would
undergo
C–N
t-BuOH
also
participates
give
C–OR
bond
This
is
divergent
from
their
at a Pd(IV) intermediate (8). The authors rule out an alternative SN2-displacement of Pd(IV) by ROH
since
t-BuOH
also participates
to give
C–OR
bond
formation.
This
is divergent
from their
reductive
elimination
in the
absence
ofusing
an
external
nucleophile
(for
discussion
bond
formation,
previous
reports
onparticipates
C–H
amination
this
same
system, where
8reactivity
wouldof
undergo
selective
since t-BuOH
also
to give
C–OR
bond
formation.
This
reactivity
isC–N
divergent
from C–N
their
see
Section
2.2.4.2,
Scheme
27b).
It
was
found
that
the
use
of
other
oxidants
including
AgOAc,
Oxone,
previous
reports
on
C–H
amination
using
this
same
system,
where
8
would
undergo
selective
C–N
reductive
elimination
in theamination
absence ofusing
an external
nucleophile
(for discussion
C–N bond
formation,
previous reports
on C–H
this same
system, where
8 wouldofundergo
selective
C–N
Ce(SO
4)elimination
2, K2S2O8, “F+in
”
sources,
as
well
as
hypervalent
iodine
oxidants
with
other
carboxylate
ligands
reductive
the
absence
of
an
external
nucleophile
(for
discussion
of
C–N
bond
formation,
see
Sectionelimination
2.2.4.2, Scheme
It was
that the
use of other
including
Oxone,
reductive
in the27b).
absence
of found
an external
nucleophile
(foroxidants
discussion
of C–N AgOAc,
bond formation,
2)–H alkoxylation, either mono- or bisalkoxylation could be
gave
inferior
conversions.
In
C(sp
+” sources,
seeall
Section
2.2.4.2,
Scheme
27b).
It
was
found
that
the
use
of
other
oxidants
including
AgOAc,
Oxone,
Ce(SO
4
)
2
,
K
2
S
2
O
8
,
“F
as
well
as
hypervalent
iodine
oxidants
with
other
carboxylate
ligands
see Section 2.2.4.2, Scheme 27b). It was found that the use of other oxidants including AgOAc, Oxone,
++”
achieved
by
altering
the
equivalents
of
PhI(OAc)
2.
2as
Ce(SO
)
,
K
S
O
,
“F
sources,
as
well
hypervalent
iodine
oxidants
with
other
carboxylate
ligands
all
gave
inferior
conversions.
In
C(sp
)–H
alkoxylation,
either
monoor
bisalkoxylation
could
be
4 2 4)2, 2K22S2O
8 8, “F ” sources, as well as hypervalent iodine oxidants with other carboxylate ligands
Ce(SO
allachieved
gave
inferior
conversions.
InInC(sp
either monomono-ororbisalkoxylation
bisalkoxylationcould
could
by altering
the equivalents
of22)–H
PhI(OAc)
2.
all
gave
inferior
conversions.
C(sp
)–H alkoxylation,
alkoxylation,
either
bebe
C(sp 3 )–H alkoxylation
achieved
byby
altering
the
equivalents
achieved
altering
the
equivalentsofofPhI(OAc)
PhI(OAc)22..
C(sp 3 )–H alkoxylation
OAc
OR
N
N
O
O
C(sp 3 )–H alkoxylationPd(OAc) 2,
N
N
OAc
ORIV
C–OR RE
PhI(OAc)
ROH
IV
2
Pd
Pd
N
N
O
O
H HN
O
Pd(OAc) 2,
RO HN
O
N
N
N
N
OAc
OR
ROH/xylenes
C–OR RE
OAc
ORIV
PhI(OAc) 2(1:4)
ROH
IV
N 2
N 2
O
O
Pd
Pd
Pd(OAc) 2,
H HN R O
RO HN R O
NN
8 NN
C–OR RE
ROH/xylenes
PhI(OAc)(1:4)
ROH
R1
OAc
OR
2
R1
Pd IV
Pd IV
H HN R 2 O
RO HN R 2 O
N
N
8
ROH/xylenes (1:4)
1
OAc
OR
R1
C(sp 2R)–H alkoxylation
R2
R2
8
R1
R1
Pd(OAc) 2,
OMe
O
O
O
C(sp 2 )–H alkoxylation
PhI(OAc) 2
2
N
N
N
or
Pd(OAc) 2,
O
O
O
R C(sp )–H alkoxylation
R
R OMe
H
H
H
PhI(OAc) 2 (1:4)
N
N
N
MeOH/xylenes
OMe
Pd(OAc) 2,
OMeOMe
N O
N O
N O
or
R
R
R
H
H
H
PhI(OAc)
N
N
MeOH/xylenes2 (1:4)
(1.5 N
equiv.)
PhI(OAc)
(2.5 equiv.)
PhI(OAc)
2N
2N
N
or
OMe
OMe
R
R
R
H
H
H
N
N
N
MeOH/xylenes (1:4)
equiv.)
equiv.)
PhI(OAc)
OMe
OMe
2 (1.5
2 (2.5
Scheme 9. C(sp3)–H alkoxylation using picolinamide
directing
group PhI(OAc)
via ligand
exchange
at Pd(IV).
PhI(OAc) (1.5 equiv.)
PhI(OAc) (2.5 equiv.)
2
Scheme 9. C(sp3)–H alkoxylation using picolinamide2 directing group via ligand
exchange at Pd(IV).
A similar transformation
has also been reported by Rao using an 8-aminoquinoline directing group
3)–H alkoxylation using picolinamide directing group via ligand exchange at Pd(IV).
3 )–H
Scheme
9. C(sp
9. C(sp
alkoxylation
using picolinamide
directing
group
via
ligand
exchange
at Pd(IV).
5-iodane Dess-Martin
andScheme
the
unique
choice
of
λ
Periodinane
(DMP,
as the
oxidant
(Scheme
10)group
[24].
A similar transformation has also been reported
by Rao using
an9)8-aminoquinoline
directing
and the
uniquetransformation
choice of λ5-iodane
Dess-Martin
Periodinane
(DMP,
as the oxidant (Scheme
10)group
[24].
A similar
has also
been reported
by Rao using
an9)8-aminoquinoline
directing
5
and the unique choice of λ -iodane Dess-Martin Periodinane (DMP, 9) as the oxidant (Scheme 10) [24].
Molecules 2017, 22, 780
8 of 54
A similar transformation has also been reported by Rao using an 8-aminoquinoline directing group
8 of 54
of 54
and the unique choice of λ5 -iodane Dess-Martin Periodinane (DMP, 9) as the oxidant (Scheme 10)8 [24].
Other
oxidants
including PhI(OAc)
PhI(OAc)2 ,PhI(OTFA)
PhI(OTFA)2,2K
,K
Selectfluor
all gave
8 , NaIO
4 , NaIO
3 , and
Otheroxidants
oxidantsincluding
including
2S22S
O28O
, NaIO
4, NaIO
3, and
Selectfluor
all gave
little
Other
PhI(OAc)22,,PhI(OTFA)
2, K2S2O8, NaIO4, NaIO3, and Selectfluor all gave little
little
or
no
conversion
to
desired
products
and
competing
functionalization
of
the
8-aminoquinoline
or no
no conversion
conversion to
to desired
desired products
products and
and competing
competing functionalization
functionalization of
of the
the 8-aminoquinoline
8-aminoquinoline
or
directing
group
was
also
observed.
The
authors
propose
that
DMP
is
not
the
terminal
oxidant
directing
group
was
also
observed.
The
authors
propose
that
DMP
is
not
the
terminal
oxidant but
but
directing group
was also observed. The authors propose that DMP is not the terminal oxidant
but
3
rather
cyclic
λλ33-iodane
10,
formed
in
situ
by
attack
of
the
alcohol
on
DMP,
which
then
transfers
the
rather
cyclic
-iodane
10,
formed
in
situ
by
attack
of
the
alcohol
on
DMP,
which
then
transfers
the
rather cyclic λ -iodane 10, formed in situ by attack of the alcohol on DMP, which then transfers the
alkoxide
to
the
palladium
center
upon
oxidation.
However,
a
similar
ligand
displacement
at
a
Pd(IV)
alkoxideto
tothe
thepalladium
palladiumcenter
centerupon
uponoxidation.
oxidation.However,
However,aasimilar
similarligand
liganddisplacement
displacementat
ataaPd(IV)
Pd(IV)
alkoxide
intermediate,
analogous
to
Chen’s
report,
cannot
be
ruled
out.
intermediate,
analogous
to
Chen’s
report,
cannot
be
ruled
out.
intermediate, analogous to Chen’s report, cannot be ruled out.
Molecules 2017, 22, 780
Molecules 2017, 22, 780
R2
R2
R1
R1
O
O
H
H
N
NH
H
N
N
Pd(OAc)
Pd(OAc) 22
DMP/ROH, 100 °C
DMP/ROH, 100 °C
R2
R2
R1
R1
OAc
AcO OAc
OAc
AcO I OAc
I
ROH
O
ROH
O
O
O
N
NH
H
OR
OR
N
N
DMP (9) O
DMP (9) O
OR
OR
I
I
O
O
10 O
10 O
Scheme10.
10. C(sp
C(sp333)–H alkoxylation of methylene positions using an 8-aminoquinoline
8-aminoquinoline directing
directing group
group
Scheme
Scheme
10. C(sp
)–H alkoxylation of methylene positions using an 8-aminoquinoline directing
group
andDMP
DMP asan
an oxidant.
and
and
DMP as
as an oxidant.
oxidant.
2.2.2.2. Alkene
Alkene Difunctionalization,
Difunctionalization, Allylic
Allylic Oxidation
Oxidation
2.2.2.2.
Alkene
Difunctionalization,
Allylic
2.2.2.2.
Oxidation
Thedifunctionalization
difunctionalization
ofalkenes
alkenes
also
possible
employing
Pd(II)/Pd(IV)
catalysisand
and
hypervalent
The
difunctionalization
of
alkenes
ispossible
also possible
employing
Pd(II)/Pd(IV)
catalysis
and
The
of
isisalso
employing
Pd(II)/Pd(IV)
catalysis
hypervalent
iodine
reagents.
Through
the
traditional
Pd(0)/Pd(II)
catalysis,
the
Pd(II)
intermediate
(11)
that
arises
hypervalent
iodine
reagents.
Through the
traditionalcatalysis,
Pd(0)/Pd(II)
catalysis,
the Pd(II)(11)
intermediate
iodine
reagents.
Through
the traditional
Pd(0)/Pd(II)
the Pd(II)
intermediate
that arises
from
initial
heteropalladation
undergoes
rapid
β-hydride
elimination
to
regenerate
an alkene
alkene
(11)
that
arises
from
initial
heteropalladation
undergoes
rapid
β-hydride
elimination
to
regenerate
from initial heteropalladation undergoes rapid β-hydride elimination to regenerate an
(Scheme
11).
By
introducing
an
appropriate
oxidant,
11
can
instead
be
oxidized
to
a
Pd(IV)
species
an
alkene
(Scheme
11).
By
introducing
an
appropriate
oxidant,
11
can
instead
be
oxidized
to
a
Pd(IV)
(Scheme 11). By introducing an appropriate oxidant, 11 can instead be oxidized to a Pd(IV) species
(12), which
which
set up
upisfor
for
subsequent
reductive
elimination.
species
(12),isis
which
setsubsequent
up for subsequent
reductive
elimination.
(12),
set
reductive
elimination.
X
X
β-hydride
β-hydride
X
X
R
R
11
11
R
R
[Pd II ]
[Pd II ]
X1
X1
[Pd IV ]
[Pd IV ]
12 X1
12 X1
X
X
[O]
[O]
R
R
alkene products
alkene products
X
X
C–X RE
C–X RE
R
R
X1
X1
difunctionalized
difunctionalized
products
products
Scheme 11. Alkene difunctionalization enabled via Pd(II)/Pd(IV) catalysis.
Scheme 11.
11. Alkene
Alkene difunctionalization
difunctionalization enabled
enabled via
via Pd(II)/Pd(IV)
Pd(II)/Pd(IV) catalysis.
Scheme
catalysis.
There have
have been
been several
several reports
reports on
on 1,2-aminooxygenation
1,2-aminooxygenation of
of alkenes
alkenes via
via this
this approach
approach that
that
There
There
have
been
several
reports
on
1,2-aminooxygenation
of
alkenes
via
this
approach
that
utilize
utilize phthalimide
phthalimide as
as the
the nitrogen
nitrogen source.
source. Stahl
Stahl reported
reported the
the use
use of
of allylic
allylic ethers
ethers in
in the
the
utilize
phthalimide
as the aminoalkoxylation
nitrogen source. Stahl
reported alkenes
the use of
allylic ethers
in the
diastereoselective
diastereoselective
of
terminal
(Scheme
12a)
[25].
Mechanistic
studies
diastereoselective aminoalkoxylation of terminal alkenes (Scheme 12a) [25]. Mechanistic studies
aminoalkoxylation
of terminal
alkenes (Scheme
12a)
[25]. Mechanistic
studies
revealed
that an
revealedthat
thatan
aninitial
initial
cisaminopalladation
aminopalladation
stepand
and
oxidation
gavePd(IV)
Pd(IV)intermediate
intermediate
13,followed
followed
revealed
cis
step
oxidation
gave
13,
initial
cis
aminopalladation
step
and
oxidation
gave
Pd(IV)
intermediate
13,
followed
by
C–O
bond
byC–O
C–Obond
bondformation
formationvia
viaan
anintermolecular
intermolecularSSNN2-displacement
2-displacementby
byacetate.
acetate.Using
Usingaasimilar
similarapproach,
approach,
by
formation
via an intermolecular
2-displacement
acetate. Using a similar
approach,
Sanford
Sanford employed
employed
homoallylicSN
alcohols
in the
the by
diastereoselective
formation
of substituted
substituted
Sanford
homoallylic
alcohols
in
diastereoselective
formation
of
employed
homoallylic
alcohols
in 12b)
the diastereoselective
formation
of substituted
tetrahydrofuran
rings
tetrahydrofuran
rings
(Scheme
[26].
Consistent
with
Stahl’s
findings,
Sanford
reports
cis
tetrahydrofuran rings (Scheme 12b) [26]. Consistent with Stahl’s findings, Sanford reports aa cis
(Scheme
12b)
[26].
Consistent
with
Stahl’s
findings,
Sanford
reports
a
cis
aminopalladation/oxidation
aminopalladation/oxidation sequence
sequence however,
however, in
in this
this case,
case, the
the presence
presence of
of the
the homoallylic
homoallylic alcohol
alcohol
aminopalladation/oxidation
sequence
however,
in thiscoordination
case, the presence
of
the homoallylic
alcohol
results
in intramolecular
results
in
intramolecular
to
give
palladacycle
14.
This
leads
to
preferential
direct
C–O
results in intramolecular coordination to give palladacycle 14. This leads to preferential direct C–O
coordination
to
give
palladacycle
14.
This
leads
to
preferential
direct
C–O
bond
forming
reductive
bond forming
forming reductive
reductive elimination
eliminationrather
rather than
thanintermolecular
intermolecularSSNN22 attack
attack on
on14.
14. Consistent
Consistentwith
with the
the
bond
elimination
rather thanofintermolecular
SN 2 attack
on 14. Consistent
withsubstitution
the necessary
formation
of
necessary
formation
the
six-membered
palladacycle,
additional
on
the
alcohol
necessary formation of the six-membered palladacycle, additional substitution on the alcohol
the
six-membered
palladacycle,
additional
substitution on the alcohol backbone results in significantly
backbone
resultsin
in
significantly
higheryields.
yields.
backbone
results
significantly
higher
higher yields.
Molecules 2017, 22, 780
9 of 54
Molecules 2017, 22, 780
9 of 54
a. Stahl (2006)
PdCl 2(CH 3CN) 2,
phthalimide
Molecules 2017, 22,
RO780
NPhth
OAc
RO
1
a.RStahl
(2006) PhI(OAc) 2
RO
O
via cis-aminopalladation/
Pd IV
AcO oxidation
O
2
–OAc
–OAc
R1oxidation
13
R1
AgBF4,
R
R= phthalimide
Ar, 54-80%
OH
alkyl,
H <30%
PhI(OAc)
O
9 of 54
SN 2
13
NPhth
SN 2
[Pd IV ]
RO
via cis-aminopalladation/
NPhth
OAc
RO
PhI(OAc) 2
Pd(OAc) 2,
AgBF4,
phthalimide
b. Sanford (2007)
OH
Pd(OAc) 2,
PhI(OAc)
2
R
R
R1
R1
PdCl 2(CH 3CN) 2,
phthalimide
b. SanfordR(2007)
1
NPhth
[Pd IV ]
RO
NPhth
R
R
O
AcO Pd IV
AcO
R
NPhth
C–O
NPhth
AcO
14
NPhth
14
reductive
elmination
C–O
reductive
elmination
Ar, 54-80%
Scheme
aminooxygenation
Scheme 12.
12.Two
Two approaches
approaches to
toR=alkene
alkene
aminooxygenation via Pd(II)/Pd(IV).
Pd(II)/Pd(IV).Changes
Changes in
insubstrate
substrate lead
lead
alkyl, H <30%
to
to aa divergence
divergence in
in mechanism
mechanism for C–O bond formation.
Scheme 12. Two approaches to alkene aminooxygenation via Pd(II)/Pd(IV). Changes in substrate lead
a divergence
in mechanism
for C–Oofbond
formation.
Dongtoreported
the
dioxygenation
alkenes
with [Pd(dppp)(H2O)2](OTf)2 and PhI(OAc)2, an
Dong reported the dioxygenation of alkenes with [Pd(dppp)(H2 O)2 ](OTf)2 and PhI(OAc)2 , an
attractive alternative to the use of toxic osmium-based reagents (Scheme 13) [27]. Based on labeling
attractiveDong
alternative
to the
thedioxygenation
use of toxic osmium-based
(Scheme
13) 2[27].
on2,labeling
reported
of alkenes with reagents
[Pd(dppp)(H
2O)2](OTf)
and Based
PhI(OAc)
an
studies
and thealternative
observedto
cisthe
diastereoselectivity,
they propose
a mechanism
involving
a Pd(II)/Pd(IV)
attractive
use
of
toxic
osmium-based
reagents
(Scheme
13)
[27].
Based
on
labeling
studies and the observed cis diastereoselectivity, they propose a mechanism involving a Pd(II)/Pd(IV)
cycle studies
and anand
SN2-type
displacement
of a Pd(IV) intermediate.
coordination gives
Pd(II) species
observed
cis diastereoselectivity,
they
proposeAlkene
a mechanism
a Pd(II)/Pd(IV)
cycle and an
SNthe
2-type
displacement
of a Pd(IV)
intermediate.
Alkeneinvolving
coordination
gives Pd(II)
15 and
promotes
intermolecular
attack
by
AcOH
to give 16,Alkene
whichcoordination
is oxidizedgives
by PhI(OAc)
2 to give
cycle
and
an
S
N2-type displacement
of
a
Pd(IV)
intermediate.
Pd(II)
species
species 15 and promotes intermolecular attack by AcOH to give 16, which is oxidized by PhI(OAc)
2 to
Pd(IV)
species
17. 17
then undergoes
intramolecular
SN2-diplacement
giving
cyclic
15 and
promotes
intermolecular
attack by
AcOH to give 16,
which is oxidizedbybyacetate
PhI(OAc)
2 to give
give Pd(IV) species 17. 17 then undergoes intramolecular SN 2-diplacement by acetate giving cyclic
Pd(IV)
17. by
17 opening
then undergoes
SN2-diplacement
bycould
acetatealso
giving
cyclic in
oxonium
18 species
followed
with Hintramolecular
2O and acylation.
This method
be applied
oxonium 18 followed by opening with H2 O and acylation. This method could also be applied in
oxonium
18 followed
by opening
2O and acylation.
This method to
could
be applied in and
substrates
possessing
tethered
alcoholwith
andHcarboxylic
acid nucleophiles
givealso
tetrahydrofuran
substrates
possessing
tethered
alcohol
acidnucleophiles
nucleophiles
give
tetrahydrofuran
substrates
possessing
tethered
alcoholand
andcarboxylic
carboxylic acid
to to
give
tetrahydrofuran
and and
lactone
products.
lactone
products.
lactone
products.
R1
R2
R1
R2
OAc OAc H O/Ac O
2 H 2O/Ac
2 2O
R2 R2
R1
OAc OAc
OAc
[Pd(dppp)(H 2O) 2](OTf)2
OAc
[Pd(dppp)(H 2O) 2](OTf)
2
R1 PhI(OAc) 2, AcOH/H
2O;
PhI(OAc) 2, AcOH/H2O;
then Ac2O
2
2
2
O - -HH2O
+
H22O
2O
+H
++
O O OO
P
P
Me
Me
1818
II
Pd
Pd II
P
P
OAc
P
OAc
OAc
[Pd(dppp)(H
2O)](OTf)
2](OTf)2
[Pd(dppp)(H O)
R1R1 RR
22
P
R1
R2
then Ac2O
P
R1
R2
OAc
R2 R2
OH
OH
2 2
R1 R
1
2+
2+
P
OH 2
Pd IVOH 2 H
P
P Pd IV
H
R2
R1
O
R
H
2
R
171
O O
17
H
OH2
P PdII
OH2
II R
1
R 2 Pd
P
R1
15 R 2
15
HOAc
O
HOAc
PhI
P
PhI
PhI(OAc) 2
PhI(OAc) 2
PP
P
Pd II
OH2
H
H
OH2
R2
R1 Pd II
H
H
16
OAc R
R1
H
2
H
16 Pd(II)/Pd(IV) catalysis.
Scheme 13. Diastereoselective catalytic alkene dioxygenation
using
OAc
Scheme 13. Diastereoselective catalytic alkene dioxygenation using Pd(II)/Pd(IV) catalysis.
Scheme
13. Diastereoselective
catalytic
alkene dioxygenation
usingable
Pd(II)/Pd(IV)
catalysis.
Using PhI(OBz)
2 and PdCl2(PhCN)
2, Sanford’s
group was also
to perform
asymmetric
alkene PhI(OBz)
dioxygenation
tethering
of a2chiral
oxime group
directing
group
14) [28]. They
were able
Using
PdCl
, Sanford’s
was
also (Scheme
able to perform
asymmetric
alkene
2 andby
2 (PhCN)
Using
PhI(OBz)
2 and
(PhCN)
2,diastereoselectivity
Sanford’s
group
was
also able
asymmetric
to achieve
moderate
to PdCl
high
on
a wide
range
of perform
oxime
dioxygenation
by
tethering
of a2levels
chiralofoxime
directing
group
(Scheme
14) to
[28].
Theysubstrates
were
able to
alkene
dioxygenation
bychiral
tethering
of a A
chiral
oxime
directing
group
(Scheme
[28].
They
were able
possessing
different
elements.
control
experiment
both
a cis
and 14)
trans
alkene
showed
achieve
moderate
to high
levels
of diastereoselectivity
on a using
wide
range
of oxime
substrates
possessing
that both
gave risetotohigh
theirlevels
respective
syn dioxygenated products,
shedding
some
light on
the
to
achieve
moderate
of
diastereoselectivity
on
a
wide
range
of
oxime
substrates
different chiral elements. A control experiment using both a cis and trans alkene showed that both
gave
potential
mechanism.
While
the
exact
pathway
was
not
elucidated,
they
propose
that
an
initial
possessing different chiral elements. A control experiment using both a cis and trans alkene showed
rise to their respective syn dioxygenated products, shedding some light on the potential mechanism.
that both gave rise to their respective syn dioxygenated products, shedding some light on the
potential mechanism. While the exact pathway was not elucidated, they propose that an initial
Molecules 2017, 22, 780
10 of 54
2017, 22, 780
10 of 54
WhileMolecules
the exact
pathway was not elucidated, they propose that an initial oxypalladation could
occur in
eitheroxypalladation
a trans or cis fashion
to
give
19
or
20,
each
of
which
can
converge
to
the
syn
product
by
either
could occur in either a trans or cis fashion to give 19 or 20, each of which can converge an
Molecules
2017,
22,
780
10 of 54
SN 2-type
direct
eliminationor
respectively.
direct reductive elimination respectively.
to thedisplacement
syn product byor
either
an reductive
SN2-type displacement
oxypalladation could occur in either a trans or cis fashion to give 19OBz
or 20, each of which can converge
PdCl 2(PhCN) 2,
O reductive
OBz elimination respectively.
or
direct
to the syn product by either an NSNO2-type displacement
N
PhI(OBz) 2
*
*Aux
R1
N
dr up to 90:10
PdCl 2(PhCN) 2,
PhI(OBz) 2
O
*Aux
OBz
O
OBz
N
*
R1
OBz
*Aux IVR1
N Pd
OBz
*Aux
R1
dr up to 90:10
trans oxypalladation/
R2
or [OBz]
oxidation
PhI(OBz) 2
N
N
O
O
[Pd] II
[Pd] II
BzO
Pd II or [OBz]
L
N O
R1
R2
BzO
Pd II
L
N O
R1
O
R1
OBz
OBz
19
R 2or [OBz]
N Pd IV OBz
O
R1
OBz
19
R 2or [OBz]
N Pd IV OBz
O
R1
OBz
20
R 2or [OBz]
N Pd IV OBz
O
trans oxypalladation/
oxidation
PhI(OBz) 2
PhI(OBz)
2
cis oxypalladation/
oxidation
PhI(OBz) 2
R2
R1
cis oxypalladation/
oxidation
S N2-type
or
Direct
reductive
S N2-type
elimination
or
N
O
OBz
syn
OBz
N
O
Direct
reductive
elimination
OBz
syn
Scheme 14. Asymmetric alkene dioxygenation using a chiral oxime directing group.
Scheme 14. Asymmetric alkene dioxygenation using a chiral
oxime directing group.
20
or [OBz]
Using a palladium NCN-pincer complex (21) or Pd(OAc)2, Szabo’s group was able to perform
Scheme 14. Asymmetric alkene dioxygenation using a chiral oxime directing group.
Using
a palladium
NCN-pincer or
complex
(21) or Pd(OAc)
was2, able
to
, PhI(OBz)
or
allylic acetoxylation,
benzoxylation,
trifluoroacetoxylation
using
PhI(OAc)2group
2 , Szabo’s
PhI(OTFA)
2 acetoxylation,
(Scheme 15) [29,30].
This offers or
a complimentary
approach using
to traditional
methods
of
perform
allylic
benzoxylation,
trifluoroacetoxylation
PhI(OAc)
, PhI(OBz)
2,
Using a palladium NCN-pincer complex (21) or Pd(OAc)2, Szabo’s group was able to 2perform
allylic functionalization
proceeding
via
Pd(0)/Pd(II)
catalysis.
Pd(0)/Pd(II)
methods
require
or PhI(OTFA)
(Scheme
15)
[29,30].
This
offers
a
complimentary
approach
to
traditional
methods
2
allylic acetoxylation,
benzoxylation, or trifluoroacetoxylation using PhI(OAc)2, PhI(OBz)2, or
stoichiometric
benzoquinone as an essential
additive tocatalysis.
activate the
allyl Pd(II) species for
of allylic
functionalization
via Pd(0)/Pd(II)
Pd(0)/Pd(II)
PhI(OTFA)
2 (Scheme 15) proceeding
[29,30]. This offers
a complimentary
approach
to traditionalmethods
methods require
of
nucleophilic
attack
and
the
use
of
a
more
electrophilic
Pd(IV)
intermediate
obviates
the need
for this
stoichiometric
benzoquinone as
an essential
to activate
the allyl
Pd(II) species
for nucleophilic
allylic functionalization
proceeding
viaadditive
Pd(0)/Pd(II)
catalysis.
Pd(0)/Pd(II)
methods
require
activation. The proposed catalytic cycle is shown in the context of acetoxylation, beginning with
as an essential
additive to obviates
activate the
allyl for
Pd(II)
for The
attackstoichiometric
and the use ofbenzoquinone
a more electrophilic
Pd(IV) intermediate
the need
thisspecies
activation.
oxidation of Pd(II) to Pd(IV) and subsequent alkene coordination to give complex 22. Pi-allyl
nucleophilic
attack
and
the
use
of
a
more
electrophilic
Pd(IV)
intermediate
obviates
the
need
for
this
proposed
catalytic cycle is shown in the context of acetoxylation, beginning with oxidation of Pd(II)
formation gives 23, which can then undergo reductive elimination to give desired product 24. It
activation.
The proposed
catalytic
cycle is shown
in complex
the context
acetoxylation,
beginning
with
to Pd(IV)
and
alkene
to give
22.ofPi-allyl
formation
gives
23,
which
should be subsequent
noted that White
hascoordination
reported a Wacker
oxidation
employing
a combination
of
Pd(OAc)
2
oxidation of Pd(II) to Pd(IV) and subsequent alkene coordination to give complex 22. Pi-allyl
can then
undergo
reductive
elimination
to
give
desired
product
24.
It
should
be
noted
that
White
and catalytic PhI(OAc)2, however mechanistic studies indicate that this does not involve direct has
formation gives 23, which can then undergo reductive elimination to give desired product 24. It
reported
a Wacker
oxidation
employing
a combination
ofwere
Pd(OAc)
catalytic PhI(OAc)2 , however
oxidation
to a Pd(IV)
intermediate
as no
ArI byproducts
observed
[31].
2 and
should be noted that White has reported a Wacker oxidation employing
a combination of Pd(OAc)
2
mechanistic
studies
indicate
that
this
does
not
involve
direct
oxidation
to
adoes
Pd(IV)
intermediate
as no
and catalytic PhI(OAc)2, howeverPd(II)
mechanistic
studies
indicate
that
this
not
involve
direct
catalyst 21
ArI byproducts
observed
[31]. asor no
Pd(OAc)
oxidation towere
a Pd(IV)
intermediate
ArI2 byproducts were observed [31].
R1
PhI(OR) 2
R2
R1
R2
R1
Pd(II) base
catalyst 21
Pd(OAc)
2 OTFA
OR =orOAc,
OBz,
PhI(OR) 2
R2
R1
base
R
AcO
24
R
AcO
Pd
Br
NMe 2
21
NMe 2
21
PhI
PhI(OAc) 2
COOMe X
PhIIV X L
AcO [Pd]
2 2
L
AcO [Pd]IV LX
OAc
23
COOMe X
AcO [Pd]IV LX
AcOH
23
AcOH
Me 2N
Pd
Br
PhI(OAc) 2
[Pd]II X2L 2
24
R
R2
OR
OR = OAc, OBz, OTFA
COOMe
[Pd]II X2L 2
L COOMe
R
Me 2N
OR
AcO [Pd]IV X2L 2
OAc
MeOOC
X
R
COOMe
R
AcO [Pd] IV XL2
MeOOC
X
22 OAc
R
COOMe
R
IV
AcO [Pd]
XL2
Scheme 15. Allylic acetoxylation, benzoxylation,
or trifluoroacetoxylation
via Pd(II)/Pd(IV) catalysis.
22
OAc
Scheme
15. Allylic
acetoxylation,
benzoxylation,or
or trifluoroacetoxylation
trifluoroacetoxylation viavia
Pd(II)/Pd(IV)
catalysis.
Scheme
15. Allylic
acetoxylation,
benzoxylation,
Pd(II)/Pd(IV)
catalysis.
Molecules 2017, 22, 780
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2.2.3. Carbon-Halogen, Carbon-Boron Bond Formation
2.2.3.One
Carbon-Halogen,
Carbon-Boron
Bond Formation
of the most interesting
transformations
enabled by high valent palladium catalysis is in
carbon-halogen
bond formation.enabled
In Pd(0)/Pd(II)
these groups
represent
One of the and
mostcarbon–boron
interesting transformations
by highcatalysis,
valent palladium
catalysis
is in
functional
handles
that undergo bond
facileformation.
oxidativeInaddition
and catalysis,
the reverse
highly
carbon-halogen
and carbon–boron
Pd(0)/Pd(II)
theseprocess
groups is
represent
disfavored.
Pd(II)/Pd(IV)
manifolds
the perfect
compliment,
allowing
the installation
of these
functional handles
that undergo
facileoffer
oxidative
addition
and the reverse
process
is highly disfavored.
valuable
atoms
into carbon
C–H functionalization.
The application
hypervalent
Pd(II)/Pd(IV)
manifolds
offer scaffolds
the perfectvia
compliment,
allowing the installation
of theseof
valuable
atoms
iodine
reagents
in this
limited by the relatively
low stability
and high
reactivity
of inthese
into carbon
scaffolds
via area
C–H is
functionalization.
The application
of hypervalent
iodine
reagents
this
reagents
that
possess
halogen
ligands.
PhICl
2
is
the
most
common
reagent
of
this
type
and
has
seen
area is limited by the relatively low stability and high reactivity of these reagents that possess halogen
the
mostPhICl
use,2 more
oftencommon
in highreagent
valent of
complex
whereas
N-halosuccinimides
ligands.
is the most
this typeisolation,
and has seen
the most
use, more often in have
high
dominated
synthetic
transformations
[2].
valent complex
isolation,
whereas N-halosuccinimides
have dominated synthetic transformations [2].
2.2.3.1. Carbon-Halogen Bond Formation
N-bromosuccinimide (NCS,
(NCS, NBS)
NBS)
In her 2004 report, Sanford shows that the use of N-chloro or N-bromosuccinimide
the directed
directed halogenation
halogenation products
for the chlorination or bromination of benzoquinoline give rise to the
[12].
In In
contrast,
thethe
useuse
of PhICl
C5-chlorinated
products
both
in good
good yield
yield(25,
(25,26,
26,Scheme
Scheme16)
16)
[12].
contrast,
of PhICl
2 gave
C5-chlorinated
products
2 gave
in
the
presence
and
absence
of
palladium,
indicating
a
direct
electrophilic
chlorination
mechanism
both in the presence and absence of palladium, indicating a direct electrophilic chlorination
as opposed as
to opposed
a C–H activation
highlights
the disadvantages
of using such
a highly
mechanism
to a C–H pathway.
activationThis
pathway.
This highlights
the disadvantages
of using
such
iodine reagent
arenefor
halogenation.
areactive
highly hypervalent
reactive hypervalent
iodinefor
reagent
arene halogenation.
Pd(OAc) 2,
NXS
MeCN, 100 °C
X = Br, Cl
N
w/ or w/o
Pd(OAc) 2
PhICl 2
via Pd(II)/Pd(IV)
C–H Activation/Oxidation
N
X
25
Cl
via Electrophilic Chlorination
N
26
Scheme
whereas PhICl
PhICl22 gives
Scheme 16.
16. N-halosuccinimide
N-halosuccinimide oxidants
oxidants give
give rise
rise to
to directed
directed C–H
C–H halogenation
halogenation whereas
gives
product of direct electrophilic chlorination.
There have been several reports of C–I bond formation using the Suarez-type iodine reagent IOAc,
There have been several reports of C–I bond formation using the Suarez-type iodine reagent
often generated via reaction of PhI(OAc)2 and I2 in situ. Yu initially demonstrated this approach in the
IOAc, often generated via reaction of PhI(OAc)2 and I2 in situ. Yu initially demonstrated this
directed iodination of unactivated primary C(sp3)–H bonds using an oxazoline
directing group (Scheme
approach in the directed iodination of unactivated primary C(sp3 )–H bonds using an oxazoline
17a) [32,33]. The use of a chiral oxazoline gave good to excellent levels of diastereoselectivity (91:9 to
directing group (Scheme 17a) [32,33]. The use of a chiral oxazoline gave good to excellent levels
99:1) in prochiral substrates. A subsequent report from Yu showed the directed α-iodination of benzoic
of diastereoselectivity (91:9 to 99:1) in prochiral substrates. A subsequent report from Yu showed
acids under similar conditions giving rise to predominantly diiodinated products (Scheme 17b) [34]. It
the directed α-iodination of benzoic acids under similar conditions giving rise to predominantly
was found that DMF was essential for high conversion and the use of tetrabutylammonium iodide as
diiodinated products (Scheme 17b) [34]. It was found that DMF was essential for high conversion
an additive could help control mono- vs. bisiodination products. While the mechanism of Pd(II)
and the use of tetrabutylammonium iodide as an additive could help control mono- vs. bisiodination
oxidation with IOAc has not been fully elucidated, KIE indicate that C–H bond cleavage is proceeding
products. While the mechanism of Pd(II) oxidation with IOAc has not been fully elucidated, KIE
via an electrophilic mechanism in these cases and thus a Pd(II)/Pd(IV) catalytic cycle is proposed.
indicate that C–H bond cleavage is proceeding via an electrophilic mechanism in these cases and thus
Kraft demonstrated the use of a Pd(II)-NHC complex for stoichiometric dichlorination of linear
a Pd(II)/Pd(IV) catalytic cycle is proposed.
alkenes and monochlorination of benzylic C–H bonds (Scheme 18) [35]. PhICl2 oxidizes Pd(II) species
Kraft demonstrated the use of a Pd(II)-NHC complex for stoichiometric dichlorination of linear
27 to Pd(IV) (28), and subsequent loss of chloride generates a cationic, pentacoordinated Pd(IV)
alkenes and monochlorination of benzylic C–H bonds (Scheme 18) [35]. PhICl2 oxidizes Pd(II) species
species that is active for C–H chlorination.
27 to Pd(IV) (28), and subsequent loss of chloride generates a cationic, pentacoordinated Pd(IV) species
that is active for C–H chlorination.
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a. Yu (2005)
a. Yu (2005)
Me
R Me
R
R
R
N
N
O
O
tBu
tBu
b. Yu (2008)
b. Yu (2008)
Me
Me
CO 2H
CO 2H
Pd(OAc) 2,
Pd(OAc) ,
PhI(OAc) 22/I2
PhI(OAc) 2/I2
Pd(OAc) 2,
Pd(OAc) 2/I
,
PhI(OAc)
2 2
PhI(OAc) 2 /I2
DMF, additive
DMF, additive
R
R
R
R
Me
Me
I
I
I
I
N
N
O
O
CO 2H
CO 2H
I
I
major w/o NBu 4I
major w/o NBu 4I
tBu
tBu
PhI(OAc) 2/I2
PhI(OAc) 2/I2
+
+
Me
Me
IOAc
IOAc
CO 2H
CO 2H
I
I
major w/ NBu4I
major
w/
NBu
4I
(15:1 mono:bis)
(15:1 mono:bis)
2
Scheme
(a) C(sp
C(sp33)–H
situ generated
generated IOAc.
Scheme 17.
17. Directed
Directed iodination
iodination of
of (a)
)–H and
and (b)
(b) C(sp
C(sp22)–H
)–H bonds
bonds using
using in
in situ
Scheme
17.
Directed
iodination
of
(a) C(sp3)–H
and
(b)
C(sp
)–H
bonds
using
in
situ generated IOAc.
IOAc.
Cl
Cl
Cl
Cl
N
N
N
N
N
N
Pd IIII
N
N
R
Pd
R
R Cl
R
Cl
Cl 27 Cl
27
PhICl 2
PhICl 2
N Cl N
N Cl N
N
N
Pd IV
N
N
R
Pd IV
R
R Cl
R
Cl
Cl Cl Cl 28
Cl
28
N
N
N
N
N
N
PdIV
N
N
IV
Pd
R
R
R Cl
R
Cl Cl
Cl
C 4H 9
C 4H 9
Cl
Cl
Cl
Cl
C 4H 9
C 4H 9
Scheme 18. Stoichiometric chlorination of linear alkenes or benzylic positions with a cationic Pd(IV)
Scheme 18.
18. Stoichiometric
Stoichiometric chlorination
of linear alkenes or benzylic positions with a cationic Pd(IV)
Scheme
chlorination
generated upon
oxidation with
PhICl2. of linear alkenes or benzylic positions with a cationic Pd(IV)
generated
upon
oxidation
with
PhICl
2.
generated upon oxidation with PhICl2 .
Direct C–H fluorination is challenging for transition metal catalysis due to the low reactivity of
Direct C–H fluorination is challenging for transition metal catalysis due to the low reactivity of
Direct
C–Hbonds
fluorination
is challenging
for transition
metal attempts
catalysis due
the low
reactivity
metal-fluorine
towards
reductive elimination.
Several
haveto been
made
using
metal-fluorine bonds towards reductive elimination. Several attempts have been made using
of
metal-fluorine
bonds
towards
elimination.
Several
attempts
have
been
using
Pd(II)/Pd(IV)
catalysis,
however
thereductive
use of hypervalent
iodine
oxidants
has been
met
withmade
challenges.
Pd(II)/Pd(IV) catalysis, however the use of hypervalent iodine oxidants has been met with challenges.
Pd(II)/Pd(IV)
the of
usethe
of hypervalent
iodine
oxidantsX-ligands,
has been met
withacetates
challenges.
This is due tocatalysis,
the highhowever
reactivity
most common
λ3-iodane
namely
or
This is due to the high reactivity of the most common λ33-iodane X-ligands, namely acetates or
This
is due
to the high
reactivityreductive
of the most
commonInλthis
-iodane
X-ligands,
namely
acetates
or
halogens,
to undergo
competitive
elimination.
area, Ritter
has been
successful
in the
halogens, to undergo competitive reductive elimination. In this area, Ritter has been successful in the
2)–H bonds
halogens,
to undergo
competitive
reductive
elimination.
In
this
area,
Ritter
has
been
successful
in
radiofluorination
of C(sp
using
stoichiometric
Pd(II)
complexes
as
fluorinating
agents
and
radiofluorination of C(sp2)–H2 bonds using stoichiometric Pd(II) complexes as fluorinating agents and
the
radiofluorination
of C(sp
bonds
using
stoichiometric
Pd(II) (poly)cationic
complexes as fluorinating
agents
a (poly)cationic
λ33-iodane
(29))–H
as the
oxidant
(Scheme
19) [36]. These
λ33-iodane reagents
a (poly)cationic λ -iodane
(29) as the oxidant (Scheme 19) [36]. These (poly)cationic λ -iodane 3reagents
and
a (poly)cationic
λ3 -iodane
(29)
as the oxidant
(Scheme
19)Dutton
[36]. These
(poly)cationic
λ -iodane
are relatively
underutilized
in the
synthetic
literature,
however
has also
used these complexes
are relatively underutilized in the synthetic literature, however Dutton has also used these complexes
reagents
underutilized
in the synthetic
literature,
however
has also
used these
to study are
highrelatively
valent palladium
and platinum
complexes
and this
work Dutton
is discussed
in Section
2.1.
to study high valent palladium and platinum complexes and this work is discussed in Section 2.1.
+
complexes
to
study
high
valent
palladium
and
platinum
complexes
and
this
work
is
discussed
in
Ritter’s report is an extension of his prior work which utilized the “F+” source Selectfluor in the two
Ritter’s report is an extension of his prior work which utilized the “F ” source+Selectfluor in the two
Section
2.1. Ritter’sofreport
is an extension
of hisaprior
workcomplex,
which utilized
the “F
source
in
step fluorination
arylboronic
acids with
similar
however
the” use
of Selectfluor
electrophilic
step fluorination of arylboronic acids with a similar complex, however the use of electrophilic
the
two step fluorination
of arylboronic
acids withto
a similar
complex,
however the
use They
of electrophilic
fluorinating
agents are not
readily translatable
radiolabeling
applications
[37].
therefore
fluorinating agents are not readily translatable to radiolabeling applications [37]. They therefore
fluorinating
agentsemploying
are not readily
translatable
to radiolabeling
applications
They therefore
designed a system
a highly
electrophilic
Pd(IV) complex
(30), could [37].
then undergo
ligand
designed a system employing a highly electrophilic Pd(IV) complex (30), could then undergo ligand
18F−. Pd(IV) complex
designed
system
employing
a highly electrophilic
Pd(IV)
complex
(30),
could
then
undergo
ligand
exchange awith
a source
of nucleophilic
30
was
accessed
via
oxidation
of
31
with
−. Pd(IV) complex 30 was accessed via oxidation of 31 with
exchange with a source of nucleophilic 18F
18 F−of
exchange
withλa33-iodane
source of
. Pd(IV)
complex
30 was
accessed
oxidation
of 31
(poly)cationic
29;nucleophilic
the key feature
this oxidant
is the
donation
of avia
labile
heterocyclic
(poly)cationic λ -iodane
29; the key feature of this oxidant is the donation of a labile heterocyclic
with
(poly)cationic
λ3 -iodane
29; the
key exchange,
feature of this
is the donation
labilesubsequently
heterocyclic
ligand
which can undergo
facile
ligand
firstoxidant
with 4-picoline
to giveof
32,a and
ligand which can undergo facile ligand exchange, first with 4-picoline to give 32, and subsequently
18F-source
ligand
which can
undergo
facile
exchange,
first
with
4-picoline
to
give
32,
and
subsequently
in
the
reaction
conditions.
This
complex
with fluoride
upon
exposure
to aligand
nucleophilic
18F-source in the reaction conditions. This complex
with fluoride upon exposure to a nucleophilic
18
with
fluoride
exposure
to a nucleophilic
F-source
in
the
reaction
conditions.
This
complex
then
then serves
asupon
a highly
electrophilic
source of 18
F
for
a
second
Pd(II)
species
(33)
which
then
undergoes
then serves as a highly electrophilic source
of 18F for a second Pd(II) species (33) which then undergoes
18
serves
as a reductive
highly electrophilic
source
of desired
F for a product.
second Pd(II)
species
(33) which
then
undergoes
C–F
C–F bond
elimination
to give
In a later
report
they also
report
the use
of
C–F bond reductive elimination to give desired product. In a later report they also report the use of
bond
reductive
elimination to process
give desired
In a later report
they also
an analogous
nickel-mediated
underproduct.
similar conditions
(see Section
5.2).report the use of an
an analogous nickel-mediated process under similar conditions (see Section 5.2).
analogous nickel-mediated process under similar conditions (see Section 5.2).
Molecules 2017, 22, 780
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Molecules 2017, 22, 780
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Molecules 2017, 22, 780
NC
NC
N I N
N
N
Pd II
31
Pd II
N
N
N
N
CN
29
N
F
Reductive
Elimination
F
Reductive
Elimination
2OTf
N
N
N
32
Me
CN
Me
F
O
Ar
S
N
O O
Ar
N Pd IISPy
N
O 33
N Pd II RPy
OTf
Ar
N
N
Pd IV N
N
N
Pd IV 32
N
N
N
30
S
O
OTf
ON Ar IV Py
S Pd
N
O
N F IV Py
Pd
N
N
2OTf
CN
=N
N
= N
N
N
O
2OTf
N
Me
N
N
Pd IV N
N
N
N
Pd IV 30
N
N
N
N
N
B
N N
N N
N
N
BN N
N N N
N
N
Me
2OTf
N
29
31
N N
CN
2OTf
N I N
N
N
13 of 54
2OTf
R
F
2OTf
N
N
N
Pd IV N
N
FPd IV
N
N
33
2OTf
N
S N2-type
fluoride transfer
S N2-type
F
fluoride transfer
18F and a (poly)cationic λ3-iodane.
Scheme19.
19.Ritter’s
Ritter’s approach
approach to
to radiofluorination
radiofluorination using
using nucleophilic
nucleophilic
18 F and a (poly)cationic
F λ3 -iodane.
Scheme
Scheme 19. Ritter’s approach to radiofluorination using nucleophilic 18F and a (poly)cationic λ3-iodane.
In catalytic Pd(II)/Pd(IV) approaches to C–H fluorination, electrophilic N-fluoropyridinium
In
catalytic
Pd(II)/Pd(IV)
approaches
to C–H than
fluorination,
electrophilic
N-fluoropyridinium
reagents
(35, 36)
have been much
more successful
the analogous
hypervalent
iodine reagent
In(35,
catalytic
Pd(II)/Pd(IV)
approaches
to C–H
fluorination,
electrophilic
N-fluoropyridinium
reagents
36)
have
been
much
more
successful
than
the
analogous
hypervalent
reagent PhIF
PhIF2 (34), as both the oxidant and fluoride source (Scheme 20a) [38,39]. Sanfordiodine
has attempted
to 2
reagents
(35,
36)
have been
much more
successful
than
the[38,39].
analogous
hypervalent
iodine reagent
(34),
as
both
the
oxidant
and
fluoride
source
(Scheme
20a)
Sanford
has
attempted
to utilize
utilize a nucleophilic fluoride source in combination with a hypervalent iodine oxidant achieve
PhIF2 (34), as both the oxidant and fluoride source (Scheme 20a) [38,39]. Sanford has attempted to
a nucleophilic
fluoride
source in(Scheme
combination
withThis
a hypervalent
oxidant achieve
catalytic
catalytic benzylic
fluorination
20b) [40].
is a much iodine
more economical
approach
as
utilize a nucleophilic fluoride source in combination with a hypervalent iodine oxidant achieve
benzylic
fluorination
20b)considerably
[40]. This isless
a much
morethan
economical
approach
as nucleophilic
nucleophilic
fluoride(Scheme
sources are
expensive
electrophilic
reagents
(e.g., 36—
catalytic benzylic fluorination (Scheme 20b) [40]. This is a much more economical approach as
fluoride
sources
considerably
less expensive
reagents
(e.g.,
$88,295/mol
vs. are
KF $3.95/mol).
A critical
challengethan
to thiselectrophilic
approach is the
relative
rates36—$88,295/mol
of competitive
nucleophilic fluoride sources are considerably less expensive than electrophilic reagents (e.g., 36—
bond forming
elimination
at Pd(IV)
(39)isrelative
to displacement
of the carboxylate
vs.C–O
KF $3.95/mol).
A reductive
critical challenge
to this
approach
the relative
rates of competitive
C–O bond
$88,295/mol−vs. KF $3.95/mol). A critical challenge to this approach is the relative rates of competitive −
ligandsreductive
by F to give
40. The use
of AgF(39)
as the
nucleophilic
fluoride source
critical
as wellby
asF
forming
elimination
at Pd(IV)
relative
to displacement
of theproved
carboxylate
ligands
C–O bond forming reductive elimination at Pd(IV) (39) relative to displacement of the carboxylate
2
to
suppress
C–O
bond
formation,
however
this
the
use
of
a
sterically
hindered
oxidant
PhI(OPiv)
to give
40.by
The
of AgF
as the
source
proved
critical
as well
as the
use as
of a
ligands
F− use
to give
40. The
use nucleophilic
of AgF as the fluoride
nucleophilic
fluoride
source
proved
critical
as well
pathway
could never
be completely
eliminated.
Therefore,
while
the
combination
of
oxidant
and
sterically
hindered
oxidant
PhI(OPiv)
to
suppress
C–O
bond
formation,
however
this
pathway
could
2
the use of a sterically hindered oxidant
PhI(OPiv)2 to suppress C–O bond formation, however this
nucleophilic
fluoride
source isTherefore,
certainly attractive,
the choice of of
oxidant
remains
challengingfluoride
and
never
be completely
eliminated.
while the
combination
oxidant
and nucleophilic
pathway
could never
be completely eliminated.
Therefore,
while the
combination
of oxidant and
continued
research
in
this
area
is
required.
source
is certainly
attractive,
theis choice
of oxidant
remains
challenging
andremains
continued
research in
this
nucleophilic
fluoride
source
certainly
attractive,
the choice
of oxidant
challenging
and
area
is
required.
continued
research in this area is required.
a. C–H fluorination with F+ oxidants
,
a. C–H fluorinationPd(OAc)
with F+ 2oxidants
"F +" source
Pd(OAc) 2,
C 6H+ 6, μwave
N
"F " source
Me
C 6H 6, μwave
N
Me
"F +" sources
F
"F +" sources
I
F F
N
N
F
F
b. C–H fluorination with oxidant/F – combination
Pd(OAc) 2,
– combination
b. C–H fluorination with oxidant/F
PhI(OR) 2, AgF
+
Pd(OAc) ,
MgSO 4, 60 2°C
N
N
N
PhI(OR) 2, AgF
+
Me
37
38
F
MgSO 4, 60 °C
N
N
N
Me
62:18 (37:38)
37
38
F
Me
BF 4–
34
3%
C–O
38
OR
OR
38
RE
C–O
RE
BF 4–
N+
Me
BF 4–
F 35
Me
N+
15%
F 35
15%
I
34
F
3%
Me
N+
Me –
BF 4
F
36
+
N
Me
75%
F
36
75%
OPiv
L
Pd IV
C OPiv
L
39
Pd IV
C
39
F–
F–
F
L
Pd IV
C F
L
40
Pd IV
C
40
Scheme 20. Complimentary approaches
to C–H fluorination with Pd(II)/Pd(IV) catalysis via (a)
62:18 (37:38)
electrophilic fluorine sources and (b) nucleophilic fluorine sources.
Scheme
Complimentary approaches
approaches to
to C–H
C–H fluorination
fluorination with
viavia
(a)(a)
Scheme
20.20.Complimentary
with Pd(II)/Pd(IV)
Pd(II)/Pd(IV)catalysis
catalysis
electrophilic fluorine sources and (b) nucleophilic fluorine sources.
electrophilic fluorine sources and (b) nucleophilic fluorine sources.
Molecules 2017, 22, 780
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Molecules 2017, 22, 780
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2.2.3.2. Carbon-Boron Bond Formation
2.2.3.2. Carbon-Boron Bond Formation
The selective
C–HC–H
borylation
of alkenes
under
oxidative
conditions
The selective
borylation
of alkenes
under
oxidative
conditionswas
wasreported
reportedby
bySzabo
Szabo in
in 2010,
giving
rise
to
valuable
alkenyl
boronates
(Scheme
21)
[41].
Using
an
NCN-pincer
Pd(II)
catalyst
2010, giving rise to valuable alkenyl boronates (Scheme 21) [41]. Using an NCN-pincer Pd(II) catalyst (21),
PhI(OTFA)
and B2 pin
borylation
of simple
alkenes
couldcould
be accomplished
in good
(21), PhI(OTFA)
2 as an oxidant,
and
B2pin
2, the borylation
of simple
alkenes
be accomplished
2 as an oxidant,
2 , the
yield.that
It isanoted
that a advantage
particular advantage
of this method
is that
the oxidizing
conditions
yield.inItgood
is noted
particular
of this method
is that the
oxidizing
conditions
produce
produceupon
TFAO-BPin
upon transmetallation
rather than borohydrides,
which
avoids competitive
TFAO-BPin
transmetallation
rather than borohydrides,
which avoids
competitive
hydroboration
hydroboration
of
the
resultant
alkene
products.
While
the
authors
could
not
fully
elucidate
of the resultant alkene products. While the authors could not fully elucidate the mechanismthe
of this
mechanism of this process, they propose that initial oxidation of catalyst 21 generates a highly
process,
they propose that initial oxidation of catalyst 21 generates a highly electrophilic Pd(IV) species
electrophilic Pd(IV) species 41 which then undergoes facile transmetallation with B2pin2 to give 42.
41 which then undergoes facile transmetallation with B2 pin2 to give 42. Alkene coordination, insertion,
Alkene coordination, insertion, and finally elimination and decomplexation give the desired products
and finally
elimination
andmethod
decomplexation
the
desired
and regenerate
Theand
method
and regenerate
21. The
is limited give
by the
need
to useproducts
solvent quantities
of the 21.
alkene,
is limited
by
the
need
to
use
solvent
quantities
of
the
alkene,
and
internal
alkenes
react
very
poorly.
internal alkenes react very poorly.
R
neat
Pd(II) 21, B 2Pin 2,
PhI(OTFA) 2
H
51-86%
Bpin
R
TFAO
R
Pd II NMe 2
Br 21
Me 2N
I
OTFA
Bpin
+
TFA-H
Me 2N
Pd II NMe 2
Br
21
PhI
TFA
Me 2N
Pd IV
R
Br
NMe 2
Br
Me 2N Pd IV NMe 2
TFAO
OTFA 41
Bpin
H
B 2pin 2
TFA
Me 2N PdIV
Bpin
Br
NMe 2
R
TFA - Bpin
Br
Me 2N Pd IV NMe 2
Bpin
OTFA 42
R
Scheme 21. C–H borylation of olefins under oxidative conditions with PhI(OTFA)2.
Scheme 21. C–H borylation of olefins under oxidative conditions with PhI(OTFA)2 .
2.2.4. Carbon-Nitrogen Bond Formation
2.2.4. Carbon-Nitrogen Bond Formation
Carbon–nitrogen (C–N) bond formation is a valuable synthetic transformation as nitrogen atoms
Carbon–nitrogen
(C–N) bond
formation
is a valuable
as nitrogen
atoms
are ubiquitous is bioactive
molecules.
Pd(0)/Pd(II)
catalysissynthetic
has servedtransformation
as a valuable approach
for the
formation of
C(sp2)–N bonds
via the
venerable Buchwald-Hartwig
amination
of arylapproach
halides. for
are ubiquitous
is bioactive
molecules.
Pd(0)/Pd(II)
catalysis has served
as a valuable
Unfortunately
wide2 )–N
spread
approaches
C–N bondBuchwald-Hartwig
formation, via either amination
C–H activation,
alkene
the formation
of C(sp
bonds
via thetovenerable
of aryl
halides.
functionalization,
or
others,
remains
a
challenge
in
palladium
catalysis.
This
is
due
both
to
the
high
Unfortunately wide spread approaches to C–N bond formation, via either C–H activation,
alkene
activation barrier for C–N bond reductive elimination from Pd(II) species and the fact that many
functionalization, or others, remains a challenge in palladium catalysis. This is due both to the high
amine substrates will coordinate to palladium, leading to rapid catalyst deactivation. Innovative
activation barrier for C–N bond reductive elimination from Pd(II) species and the fact that many amine
approaches relying on Pd(II)/Pd(IV) catalysis have emerged to address these challenges and this area
substrates
willrecently
coordinate
to palladium,
leading
to rapidiodine
catalyst
deactivation.
Innovative
has been
reviewed
by Muniz [42].
Hypervalent
reagents
have played
a key roleapproaches
in this
relying
on
Pd(II)/Pd(IV)
catalysis
have
emerged
to
address
these
challenges
and
this area
has been
area, with careful tuning of oxidant sterics and electronics playing a role in the success
a given
recently
reviewed by Muniz [42]. Hypervalent iodine reagents have played a key role in this area, with
method.
careful tuning of oxidant sterics and electronics playing a role in the success a given method.
Molecules 2017,
2017, 22,
22, 780
780
Molecules
15 of
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54
15
2.2.4.1. Alkene Diamination
2.2.4.1. Alkene Diamination
The Muniz group has been a leader in the development of both intra- and intermolecular
The Muniz
groupdiamination
has been a via
leader
in the development
of both
intermolecular
approaches
to alkene
Pd(II)/Pd(IV)
catalysis [42].
Theirintrafirst and
report
in this area
approaches
to
alkene
diamination
via
Pd(II)/Pd(IV)
catalysis
[42].
Their
first
report
in this area
involved the intramolecular diamination of terminal alkenes with urea derivatives, a particularly
involved
thetransformation
intramoleculardue
diamination
of terminal
alkenes
withofurea
derivatives,
challenging
to the high
coordinating
ability
these
substrates atoparticularly
palladium
challenging
due to
thebroad
high scope
coordinating
ability
these 1,2-diamine
substrates toproducts
palladium
(Scheme 22) transformation
[43]. Their method
had
and gave
the of
bicyclic
in
(Scheme
22)
[43].
Their
method
had
broad
scope
and
gave
the
bicyclic
1,2-diamine
products
in
excellent
excellent yields. They note that the choice of oxidant was critical and only PhI(OAc)2 was able to
yields.
They
that the
choice
oxidant was
and only
PhI(OAc)investigation
promote
thenote
reaction
with
highofefficiency.
A critical
subsequent
mechanistic
showed the
2 was able to promote
reaction with
high efficiency.
subsequent
mechanistic investigation
showed
the reaction
proceeds
via rate A
limiting
aminopalladation,
followed by
oxidation
to giveproceeds
Pd(IV)
via
rate
limiting
aminopalladation,
followed
by
oxidation
to
give
Pd(IV)
intermediate
43,
which
intermediate 43, which then undergoes SN2-type displacement by the second amine [44]. then
This
undergoes
SN 2-type
displacement
by the second
amine
[44]. in
This
catalytic
cycle is supported
by2
catalytic cycle
is supported
by stoichiometric
studies
conducted
their
group (employing
PhI(OAc)
stoichiometric
studies
conducted
in
their
group
(employing
PhI(OAc)
as
the
oxidant),
which
showed
as the oxidant), which showed that C–N bond formation proceeded
via ligand ionization and
2
that
C–N bond
formation proceeded
ionization
and subsequent
SNfrom
2-displacement
subsequent
SN2-displacement
rather via
thanligand
a concerted
reductive
elimination
Pd(IV) [45].rather
This
than
a concerted
reductive
elimination
from
Pd(IV) [45].
This general
catalytic
is invoked for
general
catalytic cycle
is invoked
for their
subsequent
applications
in both
intra-cycle
and intermolecular
their
subsequent
applications in both intra- and intermolecular amination reactions.
amination
reactions.
O
N
H
HN
Ts
Pd(OAc) 2,
PhI(OAc) 2, CH 2Cl 2
R
78-95%
R
n
O
N
O
R
R
N
N Ts
n
H
N
N Ts
O
N
Ts
Pd(OAc) 2
S N2 - type cyclization
O
N
N
Ts
OAc
PdIV
OAc
H
N
Amide
Dissociation
Pd II N
Ts
OAc
O
N
O
Ts
N
OAc
Pd IV
OAc
43
N
PhI
Oxidation
Rate-limiting
syn-aminopalladation
O
Ts
N
[Pd II ]
AcOH
PhI(OAc) 2
Scheme
22.22.
Intramolecular
N2-type displacement of a Pd(IV) intermediate.
Scheme
Intramoleculardiamination
diaminationof
of alkenes
alkenes via
via aa SSN
2-type displacement of a Pd(IV) intermediate.
Muniz extended this approach to Boc-protected guanidine substrates, which required a change
Muniz extended this approach to Boc-protected guanidine substrates, which required a change in
in oxidant from PhI(OAc)2 to stoichiometric CuCl2 (Scheme 23a) [46]. In this case, the use of PhI(OAc)2,
oxidant from PhI(OAc)2 to stoichiometric CuCl2 (Scheme 23a) [46]. In this case, the use of PhI(OAc)2 ,
a more powerful oxidant than CuCl2, gives rise to exclusively the aminoacetoxylated product as a
a more powerful oxidant than CuCl2 , gives rise to exclusively the aminoacetoxylated product as a result
result of competitive C–O reductive elimination (Scheme 23b). Furthermore, reducing the
of competitive C–O reductive elimination (Scheme 23b). Furthermore, reducing the nucleophilicity of
nucleophilicity of the terminal amine in the presence of CuCl2 led to aminochlorinated products
the terminal amine in the presence of CuCl2 led to aminochlorinated products (Scheme 23c). This SN 2
(Scheme 23c). This SN2 cyclization mechanism is also analogous to Sanford’s Pd(IV) mediated
cyclization mechanism is also analogous to Sanford’s Pd(IV) mediated cyclopropanation and these
cyclopropanation and these results clearly indicate that the further development of SN2 based
results clearly indicate that the further development of SN 2 based methods with Pd(IV) will depend on
methods with Pd(IV) will depend on careful tuning of both oxidant and nucleophile [47]. A final
careful tuning of both oxidant and nucleophile [47]. A final report of intramolecular diamination from
report of intramolecular diamination from Muniz involved the intramolecular diamination of stilbene
Muniz involved the intramolecular diamination of stilbene derivatives to yield bisindoline substrates
derivatives to yield bisindoline substrates employing Pd(OAc)2 and PhI(OAc)2 (not shown) [48].
employing Pd(OAc)2 and PhI(OAc)2 (not shown) [48].
Molecules 2017, 22, 780
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Molecules 2017, 22, 780
16 of 54
Molecules 2017,
22, 780 conditions
a. Standard
16 of 54
NBoc
a. Standard conditions
NHBoc
HN NBoc
Ph HN
NHBoc
Ph
Ph
b. Use
Ph of PhI(OAc)2
NBoc
Pd(OAc) 2,
CuCl 2
Pd(OAc) 2,
K 2CO3, DMF
CuCl 2
99%
K 2CO3, DMF
Ph
Ph
Ph
Ph
N
N Boc
NBoc
N
N Boc
99%
NBoc
b. Use of PhI(OAc)2
NHBoc
HN NBoc
Pd(OAc) 2,
PhI(OAc) 2
Pd(OAc) 2,
K 2CO3, DMF
Ph HN
NHBoc
PhI(OAc) 2
90%
Ph
K 2CO3, DMF
Ph
90% amine
Ph
c. Reduced
nucleophilicity of terminal
NBoc
Ph
Ph
Ph
Ph
N NBoc
N Boc
H
Boc
N
N
OAc
H
Fate of Pd(IV) intermediate sensitive
to choice of substrate and oxidant
Fate of Pd(IV) intermediate
sensitive
NR
to choice of substrate
R and oxidant
N NR N
X
PdRIV
N
N
X X
Pd IV
SN 2-type
C–X
X
CuCl 2
PhI(OAc) 2
SN 2-type
C–X
CuCl 2
OAc
PhI(OAc) 2
NR
NR
NBoc
NBoc
N
N NRNHR
c. Reduced nucleophilicity of terminal
Pd(OAc)amine
N R
NR
2,
CuCl 2
NH 2
HN NBoc
N NBoc
Ph
NH 2
N
N
Pd(OAc) 2,
N R
XNHR
K 2CO3, DMF
Ph
CuCl
2
Ph HN
NH 2
N
Ph
NH
85%
Cl 2
Ph
X
K 2CO3, DMF
Ph
Ph
85%
Cl
Scheme Ph
23. Intramolecular alkene diamination with guanidines.
Reactivity of Pd(IV) intermediate
Scheme 23. Intramolecular alkene diamination with guanidines. Reactivity of Pd(IV) intermediate
sensitive to both substrate and oxidant selection. (a) Standard conditions with CuCl2 as oxidant (b)
Schemeto23.
Intramolecular
alkene
diamination
guanidines.
Reactivitywith
of Pd(IV)
sensitive
both
substrate and
oxidant
selection.with
(a) Standard
conditions
CuCl2intermediate
as oxidant (b)
Use of PhI(OAc)2 as oxidant (c) Terminal amine with CuCl2.
2 as oxidant (b)
sensitive
to both
substrate
and
oxidant
selection.
(a)
Standard
conditions
with
CuCl
Use
of PhI(OAc)
as
oxidant
(c)
Terminal
amine
with
CuCl
.
2
2
Use of PhI(OAc)2 as oxidant (c) Terminal amine with CuCl2.
Extending this approach to intermolecular diamination was challenging as C–O bond forming
Extending
this approach
to intermolecular
was challenging
asintermolecular
C–O bond forming
reductive elimination
formation
would be morediamination
competitive relative
to a slower
SN2
Extending this approach to intermolecular diamination was challenging as C–O bond forming
reductive
elimination
formation
would
be
more
competitive
relative
to
a
slower
intermolecular
SN 2
amine displacement. In three reports, the Muniz group succeeded in addressing this challenge in the
reductive elimination formation would be more competitive relative to a slower intermolecular SN2
amine
displacement.
In three reports,
thealkenes,
Muniz group
succeeded
in addressing
this challenge
in the
intermolecular
diamination
of terminal
allyl ethers,
and finally
internal styrene
derivatives
amine displacement. In three reports, the Muniz group succeeded in addressing this challenge in the
intermolecular
diamination
of terminal
alkenes, allyl ethers, and finally
internal
styrene
with phthalimide,
saccharide
or N-fluoro-bis(phenylsulfonyl)imide
(NFSI)
as the
aminederivatives
sources
intermolecular diamination of terminal alkenes, allyl ethers, and finally internal styrene derivatives
(Scheme
24) [49–51].
In all cases,
PhI(OPiv)2 was employed as the hypervalent
oxidant
as
with
phthalimide,
saccharide
or N-fluoro-bis(phenylsulfonyl)imide
(NFSI) as iodine
the amine
sources
with phthalimide, saccharide or N-fluoro-bis(phenylsulfonyl)imide (NFSI) as the amine sources
PhI(OAc)
2 [49–51].
gave veryInlow
yields with
a range was
of palladium
catalysts.
The use of theiodine
more sterically
(Scheme
24)24)
employed
asthe
thehypervalent
hypervalent
oxidant
(Scheme
[49–51]. Inall
allcases,
cases, PhI(OPiv)
PhI(OPiv)22 was
employed
as
iodine oxidant
as as
encumbered
PhI(OPiv)
2 yields
is
presumably
critical
to
address
the
issue
of
competitive
C–O
reductive
PhI(OAc)
gave
very
low
with
a
range
of
palladium
catalysts.
The
use
of
the
more
sterically
2 2 gave very low yields with a range of palladium catalysts. The use of the more sterically
PhI(OAc)
elimination as the –OPiv
group will undergo
thistoprocess
much
the corresponding
–OAc,
encumbered
address
theslower
issueofthan
ofcompetitive
competitive
C–O
reductive
encumberedPhI(OPiv)
PhI(OPiv)2 2isispresumably
presumably critical
critical to
address
the
issue
C–O
reductive
allowing
intermolecular
S
N2 displacement to occur. It is noteworthy than a similar approach from
elimination
asas
the
processmuch
muchslower
slowerthan
thanthe
the
corresponding
–OAc,
elimination
the–OPiv
–OPivgroup
groupwill
willundergo
undergo this
this process
corresponding
–OAc,
Michaelintermolecular
utilized NFSI as
both
the amine source
and external
oxidant, circumventing
competitive
C–
allowing
S
2
displacement
to
occur.
It
is
noteworthy
than
a
similar
approach
from
allowing intermolecular SNN2 displacement to occur. It is noteworthy than a similar approach from
X reductive
elimination
[52,53].
Michael
utilized
NFSI
asasboth
circumventingcompetitive
competitiveC–
C–X
Michael
utilized
NFSI
boththe
theamine
aminesource
sourceand
andexternal
external oxidant,
oxidant, circumventing
Xa.reductive
elimination
[52,53].
reductive
elimination
[52,53].
b. Muniz (2011)
Muniz (2010)
a. Muniz (2010)
Pd(NCPh) 2Cl 2, saccharin,
HNTs, PhI(OPiv) 2
Pd(NCPh) 2Cl 2, saccharin,
R
HNTs,35-90%
PhI(OPiv) 2
R
35-90%
O 2S
O 2SR
R
c. Muniz (2012)
c. Muniz (2012)
R
R
R1
1
N
O
N
NTs
O
NTs
b. Muniz (2011)
R2
O
R
R2
1
O R
R
R1
Pd(NCPh) 2Cl 2, phthalimide,
(R 2SO 2) 2NH, PhI(OPiv) 2
Pd(NCPh) 2Cl 2, phthalimide,
(R 2SO 2)40-93%
2NH, PhI(OPiv) 2
Pd(hfacac) 2, phthalimide,
FN(SO 2Ph) 2, PhI(OPiv) 2
Pd(hfacac) 2, phthalimide,
40-72%
FN(SO 2Ph)
2, PhI(OPiv) 2
(R 2O2S)2N
(R 2O2S)2N
R
40-72%
O
O
O
RO
N
N2
1R
O R
R
R2
R1
O
NHTs
O
NHTs
O N
R1N
O
R
1
O
R Muniz group
40-93%
Scheme 24. Reports from the
on intermolecular alkeneRdiamination
with PhI(OPiv)2 as
the oxidant. (a) Diamination of terminal alkenes (b) Diamination of allyl ethers (c) Diamination of
Scheme 24. Reports from the Muniz group on intermolecular alkene diamination with PhI(OPiv)2 as
Scheme
24.derivatives.
Reports from the Muniz group on intermolecular alkene diamination with PhI(OPiv)2 as
styrene
the oxidant. (a) Diamination of terminal alkenes (b) Diamination of allyl ethers (c) Diamination of
the oxidant. (a) Diamination of terminal alkenes (b) Diamination of allyl ethers (c) Diamination of
styrene derivatives.
styrene
derivatives.
2.2.4.2.
C–H
Amination
2.2.4.2.
C–H Amination
Sanford
reported a study of C(sp2) and C(sp3)–H bond amination using Pd(II) catalysts and
2.2.4.2. C–H Amination
PhI=NTs as the oxidant in a stoichiometric
context (Scheme 25) [54]. Using various palladacyclic
Sanford reported a study of C(sp22) and C(sp33)–H bond amination using Pd(II) catalysts and
species
44, 45,
generated
via directed
C–H
activation,
they
found
that C–H using
insertion
happens
readily
Sanford
reported
a
study
of
C(sp
)
and
C(sp )–H
bond
amination
Pd(II)
catalysts
and
PhI=NTs as the oxidant in a stoichiometric context (Scheme 25) [54]. Using various palladacyclic
PhI=NTs
as the
oxidant invia
a directed
stoichiometric
context (Scheme
25)
[54].
Using
various
palladacyclic
species 44,
45, generated
C–H activation,
they found
that
C–H
insertion
happens
readily
Molecules 2017, 22, 780
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Molecules 2017, 22, 780
17 of 54
species 44, 45, generated via directed C–H activation, they found that C–H insertion happens readily
upon oxidation with PhI=NTs. In both cases, byproducts arising from competitive C–X bond forming
reductive elimination were observed in up to 18% yield (compounds 46, 47), and this was highly
dependent on reaction conditions. Oxidant
Oxidant electronics
electronics were
were found
found to
to play a role in the rate of C–H
insertion;
altering
the
substituents
on
the
benzylsulfonamide
PhINSO
insertion; altering the substituents on the benzylsulfonamide PhINSO
2C
5H
X(X
(X==OMe/NO
OMe/NO22 ) led to
2C
5H
44X
prolonged
from
drawing
mechanistic
conclusions
fromfrom
this this
datadata
due
prolongedreaction
reactiontimes.
times.The
Theauthors
authorsrefrain
refrain
from
drawing
mechanistic
conclusions
to
the
highly
varied
solubility
and
hydrolytic
instability
of
the
hypervalent
iodine
reagents
under
the
due to the highly varied solubility and hydrolytic instability of the hypervalent iodine reagents under
reaction
conditions.
A general
mechanism
is shown
in Scheme
25c,25c,
and
thethe
intermediacy
of of
Pd(IV)
is
the reaction
conditions.
A general
mechanism
is shown
in Scheme
and
intermediacy
Pd(IV)
supported
by theby
observation
of C–X reductive
elimination
products.
Direct C–H
activation/amination
is supported
the observation
of C–X
reductive
elimination
products.
Direct C–H
could
also be achievedcould
at sp3 C–H
however
upon
protolysis
were lower
activation/amination
also bonds,
be achieved
at isolated
sp3 C–Hyields
bonds,
however
isolated
yieldsrelative
upon
2
2
to
sp analogues.
It should
be noted
a catalyticItapproach
C–H bond
been reported
protolysis
were lower
relative
to spthat
analogues.
should betonoted
that aamination
catalytic has
approach
to C–H
using
K2 S2 O8 as has
a stoichiometric
oxidant
[55].
bond amination
been reported
using K
2S2O8 as a stoichiometric oxidant [55].
a. C(sp 2 ) C-N amination
Py
PdII
N
PhINTs
X
44 (X=Cl/OAc)
NHTs
Protolysis
NTs
N
N
N Pd Py
X
46
observed in
up to 18% yield
b. C(sp 3) C-N amination
Py
Pd II
N
NTs
PhINTs
Cl
N
Py
Pd
X
NHTs
Protolysis
N
Cl
N
45
47
X
c. Proposed general mechanism
N
C
Pd
Cl
II
Py
PhINTs
N
C
NTs
PdIV
Cl Insertion
Py
N
CN
Ts
PdII
Cl
Py
Protolysis
Pd (II) +
N
C
TsN
H
Scheme 25.
25. Stoichiometric
study of
of directed
C–H bond
bond amination
amination with
with Pd(II)
Pd(II) and
and PhI=NTs
PhI=NTs as
as oxidant
oxidant
Scheme
Stoichiometric study
directed C–H
and N-source.
N-source. Insert:
Insert: Byproducts
Byproducts observed
observed as
as aa result
result of
of competitive
competitive C–X
C–X bond
bond formation.
formation.
and
Daugulis provided the first report of catalytic alkyl-nitrogen coupling via C–H activation with
Daugulis provided the first report of catalytic alkyl-nitrogen coupling via C–H activation with
Pd(II)/Pd(IV), which relied on oxidation with PhI(OAc)2 (Scheme 26a) [56]. Other oxidants screened
Pd(II)/Pd(IV), which relied on oxidation
with PhI(OAc) (Scheme 26a) [56]. Other oxidants screened
included more electron-deficient λ33-iodanes PhI(OTFA)22, PhI(p-NO2C6H4O2C)2, as well as AgOAc, all
included more electron-deficient λ -iodanes PhI(OTFA)2 , PhI(p-NO2 C6 H4 O2 C)2 , as well as AgOAc,
of which gave very low or no conversion. The net intramolecular C–H amination proceeded via
all of which gave very low or no conversion. The net intramolecular C–H amination proceeded via
consecutive N–H/C–H activation, oxidation of complex 48 to give Pd(IV) intermediate 49, and final
consecutive N–H/C–H activation, oxidation of complex 48 to give Pd(IV) intermediate 49, and final
C–N bond forming reductive elimination. Mechanistic insights into the C–N bond forming step were
C–N bond forming reductive elimination. Mechanistic insights into the C–N bond forming step were
not provided. This work was followed closely by that of Chen who used the picolinamide directing
not provided. This work was followed closely by that of Chen who used the picolinamide directing
group for the construction of diverse 4- and 5-membered nitrogen heterocycles via C(sp3)–H
group for the construction of diverse 4- and 5-membered nitrogen heterocycles via C(sp3 )–H amination
amination (Scheme 26b) [57].
(Scheme 26b) [57].
Molecules 2017, 22, 780
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a. Daugulis (2012)
a. Daugulis (2012)
O
O
Pd(OAc) 2
Pd(OAc)
PhI(OAc) 22
PhI(OAc) 2
toluene, 80 °C
toluene, 80 °C
N
HN
H
N
N
N–H/C–H
N–H/C–H
activation
activation
O
O
[O]
[O]
N
N II
Pd
PdII
N
N
48
48
O
O
N
N
N
N
O
O
N
N IV
N
Pd
IV
N
Pd
AcO
OAc
AcO OAc
49
49
b. Chen (2012)
b. Chen (2012)
H HN
H HN
R1
R1
PA
N PA
N
N
N
N
N
O
O
R2
R2
H
H
R1
R1
HN
HN
R2
R2
R
RN
N
HN
HN
O
O
O
O
R3
R3
Pd(OAc) 2,
Pd(OAc) 2,
PhI(OAc)
2
PhI(OAc) 2
AcOH, toluene, 110 °C
AcOH, toluene, 110 °C
R1
R1
PA
NPA
N
R2
R2
R1
R1
R2
R2
R
R
N
N
PA
PA
R3
R3
C–N Reductive
C–N Reductive
Elimination
via
Elimination
via
OAc
OAc
O
O
N
Pd IVN
Pd IVN
OAc N
OAc
Scheme 26. Intramolecular C–H amination via Pd(II)/Pd(IV) catalysis with PhI(OAc)2. (a) Daugulis
Scheme
26.26.
Intramolecular
C–H
amination
with PhI(OAc)
PhI(OAc)2.2(a)
. (a)Daugulis
Daugulis
Scheme
Intramolecular
C–H
aminationvia
viaPd(II)/Pd(IV)
Pd(II)/Pd(IV) catalysis
catalysis with
3)-amination (b) Chen’s C(sp3) and C(sp2)–H amination.
report on direct C(sp
3 )-amination
33) and C(sp22 )–H amination.
3
report
on
direct
C(sp
(b)
Chen’s
C(sp
C(sp )–H amination.
report on direct C(sp )-amination (b) Chen’s C(sp
The Muniz group reported a benzylic C–H amidation via a directed C–H bond activation and
Muniz
group
reporteda abenzylic
benzylicC–H
C–Hamidation
amidation via
via a directed
C–H
bond
activation
and
TheThe
Muniz
group
reported
directed
C–H
bondmore
activation
and
subsequent
SN2-type
displacement
at Pd(IV) (Scheme
27) [58]. Ina this
reaction
it was
effective
subsequent SN2-type displacement at Pd(IV) (Scheme 27) [58]. In this reaction it was more effective
subsequent
SN 2-type
at source
Pd(IV) of
(Scheme
27)and
[58].hypervalent
In this reaction
it was
more therefore
effective to
to have the
oxidantdisplacement
also serve the
nitrogen
iodine
reagents
to have the oxidant also serve the source of nitrogen and hypervalent iodine reagents therefore
have
the oxidant
also
serve than
the source
of more
nitrogen
and deficient
hypervalent
iodinehexafluoroacetylacetonate
reagents therefore proved
proved
to be less
efficient
NFSI. A
electron
bidentate
proved to be less efficient than NFSI. A more electron deficient bidentate hexafluoroacetylacetonate
(hfacac)
ligand on
palladium
also
improved
efficiency.
reactionhexafluoroacetylacetonate
could be extended to anisole
and
to be
less efficient
than
NFSI. A
more
electron
deficientThis
bidentate
(hfacac)
(hfacac) ligand on palladium also improved efficiency. This reaction could be extended to anisole and
pyridine
directing also
groups,
giving efficiency.
a rather versatile
method
for be
C–H
bond amidation.
Despite
its
ligand
on palladium
improved
This reaction
could
extended
to anisole and
pyridine
pyridine directing groups, giving a rather versatile method for C–H bond amidation. Despite its
utility,
the
use
of
NFSI
as
the
oxidant
does
lead
to
generation
of
an
equivalent
of
HF,
and
thus
directing groups, giving a rather versatile method for C–H bond amidation. Despite its utility, the use
utility, the use of NFSI as the oxidant does lead to generation of an equivalent of HF, and thus
of oxidant
more environmentally
friendly alternatives
would of
be a significant
for
of discovery
NFSI
as the
does lead to generation
of an equivalent
and thus advancement
discovery
of more
discovery
of more environmentally
friendly alternatives
would beHF,
a significant
advancement
for
large-scale applications.
environmentally
friendly alternatives would be a significant advancement for large-scale applications.
large-scale applications.
N
N
Pd(X) 2,
Pd(X) 2,
oxidant
oxidant
1,4-dioxane
1,4-dioxane
100 °C
100 °C
Cat
Oxidant
Cat
Oxidant
PhI(OAc)NTs 2
Pd(OAc) 2
PhI(OAc)NTs 2
Pd(OAc) 2
Pd(OAc) 2
PhI(OAc) 2/HNTs2
Pd(OAc) 2
PhI(OAc) 2/HNTs2
NFSI
Pd(hfacac) 2
NFSI
Pd(hfacac) 2
N
N
NTos 2
NTos 2
Yield
Yield
54%
54%
69%
69%
95%
95%
via:
via:
N(SO 2Me) 2
N(SO 2Me) 2
N
N
OR
OR
Pd IV
Pd IVOR
X
OR
X
SN 2-type
SN 2-type
displacement
displacement
Scheme 27. Directed C(sp3)-amidation of benzylic C–H bonds via SN2-displacement of Pd(IV).
3)-amidation of benzylic C–H bonds via SN2-displacement of Pd(IV).
Scheme
Directed
C(sp
3 )-amidation
Scheme
27.27.
Directed
C(sp
of benzylic C–H bonds via SN 2-displacement of Pd(IV).
Li reported the synthesis of oxindole derivatives via a intermolecular aminopalladation/C–H
Li reported the synthesis of oxindole derivatives via a intermolecular aminopalladation/C–H
activation
cascade
Pd(OAc)
2 and PhI(OAc)2 (Scheme 28) [59]. In this case, other oxidants
Li reported
the employing
synthesis
oxindole
derivatives via a intermolecular aminopalladation/C–H
activation
cascade
employingofPd(OAc)
2 and PhI(OAc)2 (Scheme 28) [59]. In this case, other oxidants
such
as
oxone,
K
2S2O8, Cu(OAc)2, benzoquinone, and O2 were ineffective, giving little or no
activation
cascade
employing
Pd(OAc)
and
PhI(OAc)and
28) ineffective,
[59]. In thisgiving
case, other
2
2 (Scheme
such as oxone, K2S2O8, Cu(OAc)2, benzoquinone,
O2 were
little oxidants
or no
conversion to products. The authors propose either terminal C–N reductive elimination from Pd(IV)
such
as
oxone,
K
S
O
,
Cu(OAc)
,
benzoquinone,
and
O
were
ineffective,
giving
little
or
no
conversion
2 8
2
2
conversion to 2products.
The authors
propose either terminal
C–N reductive elimination from
Pd(IV)
or Pd(IV) C–H activation, however further mechanistic investigation is required.
to products.
The activation,
authors propose
either
terminal
C–N reductive
elimination
from Pd(IV) or Pd(IV)
or Pd(IV) C–H
however
further
mechanistic
investigation
is required.
C–H activation, however further mechanistic investigation is required.
Molecules 2017, 22, 780
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O
R1
O
N
R1 O
R1 N
N
O
O
ineffective oxidants screened:
Pd(OAc) 2, PhI(OAc) 2
Ar
O
O
Ar +
benzoquinone,
O 2 , Cu(OAc)
ineffective oxidants
screened:
Pd(OAc) 2, PhI(OAc) 2
2,
Ar
O
DCE,, 100
°C
ineffective
screened:
Pd(OAc)
Ar +
oxone
K2Soxidants
Ar
O
2 PhI(OAc) 2
benzoquinone,
2O 8 ,O
2 , Cu(OAc) 2,
O
Ar +
DCE, 100 °C
benzoquinone,
2 , Cu(OAc) 2,
K2S2O 8 ,Ooxone
R
N
O
DCE, 100 °C
R
K2S2O 8 , oxone
1
O
R
NR O
O
R
R
N R1
R
Scheme
28.
Synthesis
of
substituted
oxindoles
via
sequential
aminopalladation/C–H
activation.
R1
Scheme 28. Synthesis of substituted oxindoles via sequential aminopalladation/C–H
activation.
O
O
ONH
NH
ONH
N
N
N
Scheme 28. Synthesis of substituted oxindoles via sequential aminopalladation/C–H activation.
Scheme 28. Synthesis of substituted oxindoles via sequential aminopalladation/C–H activation.
The synthesis of carbazole derivatives via an oxidative C–H amidation procedure with Pd(OAc)2
The
of
derivatives
via an
C–H
amidation procedure
with Pd(OAc)
22
The synthesis
synthesis
of carbazole
carbazole
derivatives
an oxidative
oxidative
C–H
procedure
and PhI(OAc)
2 at ambient
temperature
was via
reported
by Gaunt
in amidation
2008 (Scheme
29) [60].with
ThisPd(OAc)
protocol
The synthesis
of
carbazole
derivatives
via
an
oxidative
C–H
amidation
procedure
with
Pd(OAc)
2
and
PhI(OAc)
at
ambient
temperature
was
reported
by
Gaunt
in
2008
(Scheme
29)
[60].
This
protocol
22 at ambient
and PhI(OAc)
temperature
was reported by Gaunt
in 2008
(Scheme
[60]. This
protocol
offers
an alternative
to Ulmann
and Buchwald-Hartwig
coupling
reactions
and 29)
obviates
the need
for
and
PhI(OAc)
2 at ambient temperature was reported by Gaunt in 2008 (Scheme 29) [60]. This protocol
offers
Ulmann
and
Buchwald-Hartwig
coupling
reactions and
obviates
the
offers an
an alternative
alternative to
toThe
Ulmann
andmechanism
Buchwald-Hartwig
coupling
obviates
the need
need for
for
prefunctionalization.
reaction
should proceed
asreactions
the otherand
examples
demonstrated
offers an alternative to
Ulmann
and
Buchwald-Hartwig
coupling
reactions
and obviates
the need for
prefunctionalization.
The
reaction
mechanism
should
proceed
as
the
other
examples
demonstrated
in
prefunctionalization.
reaction
the other
examples
demonstrated
in
this review. The The
isolation
of mechanism
a trinuclearshould
Pd(II) proceed
complexas(50)
having
two cyclopalladated
prefunctionalization.
Theofreaction
mechanism
should(50)
proceed
astwo
thecyclopalladated
other examplesaminobiphenyl
demonstrated
this
review.
The
isolation
a
trinuclear
Pd(II)
complex
having
in this review. connected
The isolation
of a bridging
trinuclearacetates
Pd(II) complex
(50)Pd(II)
having
two cyclopalladated
aminobiphenyl
through
to a third
suggests
the oxidation
in this review.
Thebridging
isolation
of a trinuclear
Pd(II) suggests
complex the
(50)oxidation
having two
cyclopalladated
connected
through
acetates
to
a
third
Pd(II)
pathways
leads
to
a
aminobiphenyl
connected
through
bridging
acetates
to
a
third
Pd(II)
suggests
oxidation
pathways leads to a Pd(IV) that promotes the reductive elimination. However it is alsothe
possible
that
aminobiphenyl
connected
through
bridging acetates
to
a also
third
Pd(II) that
suggests
the oxidation
Pd(IV)
that
promotes
the
reductive
elimination.
However
it
is
possible
the
trimeric
complex
pathways
to a Pd(IV)
that promotes
the reductive
However it is also possible that
the
trimericleads
complex
dissociates
into monomeric
species elimination.
prior to the oxidation.
pathways leads
to a Pd(IV) species
that promotes
elimination. However it is also possible that
dissociates
monomeric
prior
tothe
thereductive
oxidation.
the trimericinto
complex
dissociates into
monomeric
species prior to the oxidation.
the trimeric complex dissociates into monomeric species prior to the oxidation.
H
N R
H
N R
H
N R
Pd(OAc) 2 (5-10 mol%)
PhI(OAc)(5-10
, PhMe,
rt
Pd(OAc)
mol%)
2 2
Pd(OAc)
mol%)
PhI(OAc)
2 (5-10
2, PhMe, rt
PhI(OAc) 2, PhMe, rt
Directed C–H
Activation
Directed
C–H
Directed
C–H
Activation
OAc
Activation
II
PdOAc
OAc
OAc
II
Pd
N
OAc
R
Pd II OAc
N
N R
R
PhI(OAc) 2
PhI(OAc) 2
PhI(OAc) 2
N R
N R
N R
Me
Me
Me
C–N Reductive
Elimination
C–N
Reductive
C–N
Reductive
Elimination
OAc
Elimination
OAc
OAc
IV
Pd
OAcOAc
OAc
IVOAc
OAc
OAc
NR Pd
IV
Pd
NR OAc OAc
NR OAc
O
OO
O
OO
Me OO
O
Me O O
Ph
Me
N
O
Ph N
Ph N
HN
HN
II
PdHN
O
O
PdIIII
Pd II O Me
Pd
O
II O
O O
IIII
Me
O
Pd
O
Pd
O
Me
PdII
O O
PdII
50
Pd
50
50
Me
Me
Me
Isolated trimetallic Pd(II) complex
Isolated trimetallic Pd(II) complex
Isolated trimetallic Pd(II) complex
Scheme 29. Direct C(sp2)-amination at ambient temperature via Pd(II)/Pd(IV).
Scheme29.
29.Direct
DirectC(sp
C(sp22)-amination
)-aminationat
atambient
ambienttemperature
temperaturevia
viaPd(II)/Pd(IV).
Pd(II)/Pd(IV).
Scheme
Scheme 29. Direct C(sp2)-amination at ambient temperature via Pd(II)/Pd(IV).
Gaunt also reported the synthesis of aziridines through C–H activation with Pd(OAc)2 and
Gaunt
also reported
the synthesis
of aziridines
through C–H
activation
Pd(OAc)
2 and
PhI(OAc)
2 (Scheme
30). Mechanistic
experiments
demonstrated
that the
reactionwith
proceeds
through
Gaunt
Gaunt also
also reported
reported the
the synthesis
synthesis of
of aziridines
aziridines through
through C–H
C–H activation
activation with
with Pd(OAc)
Pd(OAc)22 and
and
PhI(OAc)2 of
(Scheme
30). Mechanistic
experiments
demonstrated
that the
reaction
proceeds
through
formation
a
relatively
rare
four-membered
palladacycle
(51),
which
further
reductively
eliminates
PhI(OAc)
(Scheme
30).
Mechanistic
experiments
demonstrated
that
the
reaction
proceeds
through
PhI(OAc)22 (Scheme 30). Mechanistic experiments demonstrated that the reaction proceeds through
formation
a relatively
rare four-membered
palladacycle
(51), which
further reductively
to
generateofathe
C–N bond.
Those experiments
also suggest
thatfurther
cyclopalladation
is eliminates
the rateformation
(51),
which
reductively
eliminates
to
formationof
of arelatively
relativelyrare
rarefour-membered
four-memberedpalladacycle
palladacycle
(51),
which
further
reductively
eliminates
to generate step,
the C–N
bond.byThose
experiments
also suggest
cyclopalladation
is the
ratedetermining
followed
fast
oxidation
by
PhI(OAc)
2. Theythat
subsequently
translated
this
to
a
generate
the C–N
bond.bond.
Those Those
experiments
also suggest
cyclopalladation
is the rate-determining
to generate
the C–N
experiments
also that
suggest
that cyclopalladation
is the ratedetermining
step,
followed
by fast and
oxidation
by approach
PhI(OAc)2to
. They
subsequently
translated this
to a
flow
process
providing
an
elegant
efficient
the
synthesis
of
challenging
strained
step,
followedstep,
by fast
oxidation
by PhI(OAc)
. They
subsequently
translated this
to a flowthis
process
determining
followed
by fast
oxidation2 by
PhI(OAc)
2. They subsequently
translated
to a
flow process
providing
an elegant and efficient approach to the synthesis of challenging strained
nitrogen
heterocycles
[61].
providing
an providing
elegant and
efficientand
approach
the synthesis
challenging
strained nitrogen
flow process
an elegant
efficienttoapproach
to theof
synthesis
of challenging
strained
nitrogen heterocycles [61].
heterocycles
[61].
nitrogen heterocycles
[61].
H
N
H
N H
O
CH3
NR
O
1CH 3
O O RCH3
1
O R1
O
5mol% Pd(OAc) 2
5mol% Pd(OAc)
2
PhI(OAc)
2, Ac2O
5mol% Pd(OAc)
2
70
80
°C
PhI(OAc) 2, Ac2O
PhI(OAc)
Ac2O
40-81%
70
- 802, °C
70
- 80 °C
40-81%
40-81%
N
N
O
NR
O
1
O O R
1
O R1
O
OAc
H
OAcOAc
H
NH Pd
IV
OAc
OAc
L
N Pd IV OAc
O
N Pd
IV L
OAc
O
R
L
O O 1
OAc51
R1
OAc
51
O Rfour-membered
Proposed
51
O 1state palladacycle
highProposed
oxidation
four-membered
Proposed
four-membered
high oxidation state palladacycle
high oxidation state palladacycle
Scheme 30. C–H activation approach to aziridines through high oxidation Pd(IV).
Scheme 30. C–H activation approach to aziridines through high oxidation Pd(IV).
through high
high oxidation
oxidation Pd(IV).
Pd(IV).
Scheme 30. C–H activation approach to aziridines through
Molecules 2017, 22, 780
20 of 54
2017, 22,
780
2.2.5.Molecules
C–C bond
Formation
20 of 54
20 of 54
Molecules 2017, 22, 780
2.2.5.
C–C bond Formation
2.2.5.1.
Diaryliodonium
Salts
2.2.5. C–C bond Formation
For
many
years, diorganoiodine
(III) compounds, represented [Ar–I–R]X− , have been utilized
2.2.5.1.
Diaryliodonium
Salts
2.2.5.1. Diaryliodonium
Salts
for catalytic
C–C bond formation
via oxidative transfer of “R+ ” to a Pd(0) catalyst and subsequent
For many years, diorganoiodine (III) compounds, represented [Ar–I–R]X−, have been utilized for
−, have been
reductiveFor
elimination
[62]. In recent (III)
years,
these reagents
have been extended
to Pd(II) catalysis,
compounds,
for
catalyticmany
C–C years,
bond diorganoiodine
formation via oxidative
transferrepresented
of “R+” to [Ar–I–R]X
a Pd(0) catalyst
and utilized
subsequent
+
in both
stoichiometric
and
catalytic
studies,
proceeding
via
either
Pd(III)
or
Pd(IV)
intermediates.
catalytic
C–C
bond
formation
via
oxidative
transfer
of
“R
”
to
a
Pd(0)
catalyst
and
subsequent
reductive elimination [62]. In recent years, these reagents have been extended to Pd(II) catalysis, inFrom
2 –sp
3these
reductive
elimination
[62].
In 2recent
years,
have Pd(III)
been have
extended
Pd(II) catalysis,
in
this work,
a variety
of C(sp
) and
C(spproceeding
–sp2 )reagents
bond
beentointermediates.
reported.
both stoichiometric
and
catalytic
studies,
viaformations
either
or Pd(IV)
From
both stoichiometric and catalytic
via either Pd(III) or Pd(IV) intermediates. From
2
2 studies, proceeding
3
2
this work, a variety of C(sp –sp ) and C(sp –sp ) bond formations have been reported.
Stoichiometric
this work, aStudies
variety of C(sp2–sp2) and C(sp3–sp2) bond formations have been reported.
2.2.5.1.1.
Stoichiometric
Studiesof the seminal reports on the isolation of various Pd(IV) and Pt(IV)
Canty
has
conducted many
2.2.5.1.1. Stoichiometric Studies
complexesCanty
via oxidation
with
both aryl
and
alkynyliodonium
(Scheme
31) [63–66].
ThePt(IV)
iodonium
has conducted many
of the
seminal
reports on thesalts
isolation
of various
Pd(IV) and
Canty
has
conducted
many
of
the
seminal
reports
on
the
isolation
of
various
Pd(IV)
and
Pt(IV)
salts complexes
were able to
oxidize
complexes
with a varietysalts
of ligand
scaffolds,
giving
rise to
viacleanly
oxidation
with Pd(II)
both aryl
and alkynyliodonium
(Scheme
31) [63–66].
The
complexes
via
oxidation
with
both
aryl or
and
alkynyliodonium
saltsdimer
(Scheme
[63–66].
The
iodonium
salts
able to
cleanly
oxidize
Pd(II)
complexes
a variety
of ligand
scaffolds,
giving
varying
degrees
ofwere
cis/trans
isomers
(52-cis
52-trans)
andwith
a Pd(III)
(53),31)
at low
temperature.
iodonium
salts were
able to
Pd(II)
complexes
with a variety
of ligand
scaffolds,
rise to varying
degrees
ofcleanly
cis/trans
isomers
(52-cis
or 52-trans)
and awith
Pd(III)
dimer
(53), giving
atinlow
For characterization
purposes
theseoxidize
complexes
were
then
treated
NaI
resulting
triflate
rise
to
varying
degrees
of
cis/trans
isomers
(52-cis
or
52-trans)
and
a
Pd(III)
dimer
(53),
at low
temperature.
For
characterization
purposes
these
complexes
were
then
treated
with
NaI
resulting
in of
displacement or addition into the cationic Pd(III) species (54-cis or 54-trans), and a summary
temperature.
For characterization
purposes
these complexes
were(54-cis
then treated
with NaI
resulting
in
triflate
displacement
or
addition
into
the
cationic
Pd(III)
species
or
54-trans),
and
a
summary
the complexes
synthesized
via this into
approach
is provided
below (54-cis
(55–59,orScheme
32).
Throughout
these
triflate
displacement
or addition
cationic is
Pd(III)
species
54-trans),
and Throughout
a summary
of the complexes
synthesized
via thisthe
approach
provided
below (55–59,
Scheme 32).
reports,
Canty
notes that
the palladium
complexes
are
significantly
less stable
than the
corresponding
of
the
complexes
synthesized
via this
provided
below
(55–59,
Scheme
Throughout
these
reports, Canty
notes that
the approach
palladiumis complexes
are significantly
less 32).
stable
than the
platinum
species
meaning
isolation
andpalladium
characterization
were
much
more challenging.
For athe
further
these
reports,
Canty
notes
that
the
complexes
are
significantly
less
stable
than
corresponding platinum species meaning isolation and characterization were much more challenging.
discussion
of
the
analogous
platinum
components
to
Canty’s
studies,
see
Section
3.1.
corresponding
platinum
species
meaning
isolation
and
characterization
were
much
more
challenging.
For a further discussion of the analogous platinum components to Canty’s studies, see Section 3.1.
For a further discussion of the analogous platinum components to Canty’s studies, see Section 3.1.
[IAr 2]OTf
[IAr 2or
]OTf
[PhICor CR]OTf
R
RR
R
R
RR
R
[PhIC
–60CR]OTf
°C
–60 °C
PdII
PdII
R 2 = –Ph, C CR
R 2 = –Ph, C CR
R2
R
R 2 IV
R RPdIV
Pd
or
R2
R
IV
IV
Pd
Pd
or
OTf
OTf
R2
52-trans
52-cis
OTf
OTf
52-trans
52-cis
R2
OTf
R R 2 III
OTf
Pd
R
R
III
RR Pd
Pd III
RR
Pd III
R
53
53
Ph
R Ph
PdIV N
RR PdIV NN
I
R
N
R = Ph, Me
55
I
55 R = Ph, Me
Ph
Ph IV N
Pd
N
PdIV N
I
N
I
56
56
Me
Me
Me
Me
CR
CR
Pd IV N
N
Pd IV N
I
N
I
57
57
All complexes detected by 1 H-NMR
All complexes detected by 1 H-NMR
NaI
25
NaI°C
25 °C
R
RR
R
R2
R 2 IV
Pd
IV
Pd
I
R
R RPdIV
or
R2
R
IV
Pd
or
I
R2
I54-cis
54-cis
I54-trans
54-trans
CO 2R
CONMe
2R 2
IV I2
NMe
Pd
IV
Pd2 I
NMe
NMeC2
58
CCR
58
CR
CR
CR
Me
Me
Me
Me
PdIV
PdIV
I
59 I
59
Me 2
P
Me
2
P
P
Me
P 2
Me 2
Scheme 31. Synthesis of Pd(IV) species upon oxidation with diaryl- and alkynyl iodonium salts.
Scheme
31. Synthesis of Pd(IV) species upon oxidation with diaryl- and alkynyl iodonium salts.
Scheme 31. Synthesis of Pd(IV) species upon oxidation with diaryl- and alkynyl iodonium salts.
a.
a.
R
R
b.
b.
Pd(OAc) 2 (5 mol%)
R1 Pd(OAc)
[Mes-I-Ar]BF
4
2 (5 mol%)
R1
[Mes-I-Ar]BF 4
solvent, 100 °C,
8-24
hr °C,
solvent,
100
8-24 hr
N
N
N
N
Pd II
Pd II
R
R
N
N
Ar
Ar
Ac
[Mes-I-Ar]BF 4
O
Ac
N
[Mes-I-Ar]BF 4
O
N
2
Ar
2
Ar
rate identical to use of Pd(OAc)2
rate identical to use of Pd(OAc)2
R1
R1
- reaction also applicable to
pyrrolidinone,
quinoline,to
- reaction
also applicable
and oxazolidinone
pyrrolidinone, directing
quinoline,groups
and
oxazolidinone
directing
groups
- Benzylic
sp3 bonds
also reactive
- Benzylic sp3 bonds also reactive
<1%
Pd(OAc) 2 (5 mol%)
<1%
Ph–I or
Ph–OTf
Pd(OAc)
(5
mol%)
2
N
N
Ph–I or Ph–OTf
N
N
solvent, 100 °C,
Ph
8-24
hr °C,
solvent,
100
Ph
8-24 for
hr Pd(0) oxidative addition
no reaction with substrates
no reaction with substrates for Pd(0) oxidative addition
Scheme 32. (a) Directed C–H arylation with diaryliodonium salts and Pd(OAc)2; (b) Evidence for
Scheme 32. (a) Directed C–H arylation with diaryliodonium salts and Pd(OAc)2; (b) Evidence for
Pd(II)/Pd(IV)
pathway.C–H arylation with diaryliodonium salts and Pd(OAc)2 ; (b) Evidence for
Scheme
32. (a) Directed
Pd(II)/Pd(IV) pathway.
Pd(II)/Pd(IV) pathway.
Molecules 2017, 22, 780
21 of 54
Catalytic Applications
Molecules 2017, 22, 780
of 54
In
2005, Sanford reported a directed C–H arylation using diaryliodonium salts and 21
Pd(OAc)
2,
the first report of C–H arylation invoking a Pd(II)/Pd(IV) catalytic manifold (Scheme 32a) [67].
2.2.5.1.2. Catalytic Applications
The reaction was applicable to a wide range of heterocyclic directing groups and a range of
In 2005, Sanford
reported a directed
C–H
arylation
using diaryliodonium
salts and
2,
electron-deficient
and electron-rich
aryl rings
could
be transferred
in good yields.
ThisPd(OAc)
method
was
the first report of C–H arylation3 invoking a Pd(II)/Pd(IV) catalytic manifold (Scheme 32a) [67]. The
further extended to benzylic C(sp )–H arylation on C8-methylquinoline as well as the regioselective
reaction was applicable to a wide range of heterocyclic directing groups and a range of electronarylation of 2,5-disubstituted pyrroles (not shown) [68]. This group subsequently reported a variant
deficient and electron-rich aryl rings could be transferred in good yields. This method was further
usingextended
polymer-supported
iodonium
saltsonthat
gave equally high
yields
and
the hypervalent
iodine
3)–H arylation
to benzylic C(sp
C8-methylquinoline
as well
as the
regioselective
arylation
reagent
could
be
readily
recycled
[14].
The
reaction
was
proposed
to
proceeded
via
a
Pd(IV)
of 2,5-disubstituted pyrroles (not shown) [68]. This group subsequently reported a variant using
intermediate
by analogy
to their salts
work
with
C–H
acetoxylation
Section
2.2.2.1),iodine
and preliminary
polymer-supported
iodonium
that
gave
equally
high yields (see
and the
hypervalent
reagent
could beinvestigations
readily recycledsupported
[14]. The reaction
was proposed
to proceeded
a Pd(IV) intermediate
by
mechanistic
this hypothesis
(Scheme
32b). via
A subsequent
study revealed
analogy
to
their
work
with
C–H
acetoxylation
(see
Section
2.2.2.1),
and
preliminary
mechanistic
further mechanistic insights, including that oxidation by the diaryliodonium salt was turnover
investigations
supported
this interesting
hypothesis since
(Scheme
32b). A acetoxylation
subsequent study
revealed
limiting
[69]. This is
particularly
analogous
reaction
withfurther
PhI(OAc)2
mechanistic
insights,
including
that
oxidation
by
the
diaryliodonium
salt
was
turnover
limiting
are found to be zero-order in PhI(OAc)2 and that cyclopalladation is turnover limiting. This[69].
implies
This is particularly interesting since analogous acetoxylation reaction with PhI(OAc)2 are found to be
that oxidation by diaryliodonium salts is much slower than by PhI(OAc)2 and this could be significant
zero-order in PhI(OAc)2 and that cyclopalladation is turnover limiting. This implies that oxidation by
in the further development of this chemistry as undesirable side reactions could begin to compete
diaryliodonium salts is much slower than by PhI(OAc)2 and this could be significant in the further
with development
oxidation. Aofcomplete,
detailed
mechanistic
wascould
laterbegin
conducted
between
the groups of
this chemistry
as undesirable
sidestudy
reactions
to compete
with oxidation.
Sanford,
Canty, and
Yates,mechanistic
incorporating
studies,
and readers
are directed
to Canty,
that report
A complete,
detailed
studycomputational
was later conducted
between
the groups
of Sanford,
for further
discussion
[70]. computational studies, and readers are directed to that report for further
and Yates,
incorporating
discussion
In
2006, [70].
Sanford reported of the C2-arylation of indoles using diaryliodonium salts
of the
C2-arylation
of indoles
using diaryliodonium
saltscycle
(Scheme
33)
(Scheme In
33)2006,
[71].Sanford
The reported
proposed
mechanism
invoked
a Pd(II)/Pd(IV)
catalytic
beginning
The proposed mechanism
invoked a followed
Pd(II)/Pd(IV)
cycleaddition
beginningtowith
rate-determining
with [71].
rate-determining
cyclopalladation,
bycatalytic
oxidative
give
Pd(IV) species 60
cyclopalladation, followed by oxidative addition to give Pd(IV) species 60 and subsequent C–C
and subsequent
C–C reductive elimination. This approach improved upon prior reports using
reductive elimination. This approach improved upon prior reports using Pd(0)/Pd(II), which required
Pd(0)/Pd(II), which required long reaction times and high temperatures (12–24 h, >125 ◦ C), by
long reaction times and high temperatures (12–24 h, >125 °C), by accelerating rate-determining
accelerating
rate-determining cyclopalladation through use of a Pd(II) catalyst. The use of IMes (61) as
cyclopalladation through use of a Pd(II) catalyst. The use of IMes (61) as an ancillary ligand improved
an ancillary
ligand
stabilizing but
the Pd(IV)
butsupporting
slowed reaction
conversion
by improved
stabilizing conversion
the Pd(IV) by
intermediate,
slowed intermediate,
reaction times,
a
times,mechanism
supporting
a
mechanism
wherein
electrophilic
palladation
is
rate-limiting.
wherein electrophilic palladation is rate-limiting.
R
IMesPd(OAc) 2
[Ar 2I]BF 4
H
R
R
AcOH, 25 °C-60 °C
N
Prior reports: Pd(0)/Pd(II)
12-24hr, >125 ° C
N
H
N
MesI
Pd(OAc) 2
OAc
MesI
- AcOH
Electrophilic
cyclopalladation
Pd II
[Ar 2I]BF 4
OAc
PdIV
MesI
Ph
N
Oxidation
N
Reductive
Elimination
N
Pd(II)
60
Me
Me
Me
Me
N
IMes =
Me
N
Me
61
Scheme 33. Facile C2-arylation of indoles with diaryliodonium salts through Pd(II)/Pd(IV) catalytic cycle.
Scheme 33. Facile C2-arylation of indoles with diaryliodonium salts through Pd(II)/Pd(IV)
catalytic cycle.
In a systematic study of ligand effects on regiocontrol in non-directed C–H activation, Sanford
examined the C–H arylation of naphthalene with Pd(II) and diaryliodonium salts (Scheme 34) [72]. It
In
a systematic
ligandtoeffects
regiocontrol
in non-directed
C–H
activation, Sanford
was
found that study
subtle of
changes
ligandon
sterics
had dramatic
effects on the
regioselectivity
of
examined
the using
C–H arylation
naphthalene
withligands.
Pd(II) and
diaryliodonium
salts (Scheme
34) [72].
arylation
a range ofofbidentate
diamine
Similar
to previous reports,
mechanistic
revealed
oxidation
was rate-limiting,
however in
this case
it precedes
C–H activation,
It wasinvestigations
found that subtle
changes
to ligand
sterics had dramatic
effects
on the
regioselectivity
of arylation
thenofoccurs
at a Pd(IV)
center.
usingwhich
a range
bidentate
diamine
ligands. Similar to previous reports, mechanistic investigations
revealed oxidation was rate-limiting, however in this case it precedes C–H activation, which then
occurs at a Pd(IV) center.
Molecules 2017, 22, 780
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22 of 54
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22 of 54
[Pd]II
II
[Ar[Pd]
2I]BF 4
[Ar 2I]BF 4
NO 2Ph,
2Ph,
130NO
°C,
16 hr
130 °C, 16 hr
Ligand
Ligand
64
64
65
65
66
66
Ph
Ph
Ph
Ph
+
+
62
62
9
9
27
27
71
71
[Pd]II
[Pd]II
Me
Me
Me
Me
63
63
1
1
1
1
1
1
Cl
Cl
Me
Me
tBu
tBu
Cl
Cl
N
N
Cl
Pd Cl
Pd Cl
N
Me
Cl
N
Me
Cl
Cl
tBu
Cl
Cl
tBu
64
65
64
65
Ligand sterics greatly influences regioselectivity
Ligand sterics greatly influences regioselectivity
N
N
N
N
Cl
Pd Cl
Pd Cl
Cl
N
N
N
N
Cl
Pd Cl
Pd Cl
Cl
66
66
Scheme
34.
Ligand-controlled
regioselectivity
in
non-directed
C–H arylationwith
with diaryliodoniumsalts.
salts.
Scheme34.
34.Ligand-controlled
Ligand-controlledregioselectivity
regioselectivityin
in non-directed
non-directed C–H
Scheme
C–Harylation
arylation withdiaryliodonium
diaryliodonium salts.
2.2.5.2. Benzoiodoxolones
2.2.5.2. Benzoiodoxolones
In 2013, Waser reported the direct C2-alkynylation of indoles using 1-[(triisopropylsilyl)ethynyl]In 2013,
2013,Waser
Waserreported
reported
direct
C2-alkynylation
of indoles
using 1-[(triisopropylsilyl)
thethe
direct
C2-alkynylation
of indoles
using 1-[(triisopropylsilyl)ethynyl]1λ33,2-benziodoxol-3(1H)-one
(TIPS-EBX, 67) as both an alkynyl transfer reagent and oxidant (Scheme
3
ethynyl]-1λ
,2-benziodoxol-3(1H)-one
(TIPS-EBX,
67)an
asalkynyl
both antransfer
alkynylreagent
transferand
reagent
and(Scheme
oxidant
1λ ,2-benziodoxol-3(1H)-one
(TIPS-EBX,
67) as both
oxidant
35) [73]. The authors have worked extensively with this reagent with further applications in
(Scheme
[73].
The authors
have worked
extensively
reagent
withfurther
furtherapplications
applications in
35) [73]. 35)
The
authors
have worked
extensively
withwith
thisthis
reagent
with
Au(I)/Au(III) catalysis (see Section 4.3). This method is proposed to proceed through a Pd(II)/Pd(IV)
Au(I)/Au(III)
catalysis (see
(see Section
Section 4.3). This
This method is proposed to proceed through
Au(I)/Au(III) catalysis
through aa Pd(II)/Pd(IV)
Pd(II)/Pd(IV)
catalytic cycle highly analogous to that proposed for C–H arylation (see previous discussion). This
catalytic cycle
cycle highly
highlyanalogous
analogoustotothat
that
proposed
C–H
arylation
previous
discussion).
proposed
for for
C–H
arylation
(see (see
previous
discussion).
This
approach addresses issues of C2/C3 selectivity in prior methods and products are obtained in
This
approach
addresses
issues
of C2/C3
selectivity
in prior
methods
products
obtained
approach
addresses
issues
of C2/C3
selectivity
in prior
methods
andand
products
areare
obtained
in
moderate to good yield.
in
moderate
good
yield.
moderate
to to
good
yield.
R
R
N
NR1
R1
H
H
Pd(MeCN) 4(BF 4) 2 (2 mol%)
Pd(MeCN)
(2 mol%)
4(BF(3
4) 2equiv.)
TIPS-EBX
TIPS-EBX (3 equiv.)
CH 2Cl2/H2O, rt
CH 2Cl2/H2O, rt
41–72% yield
41–72% yield
R
R
N
NR1
R1
TIPS
TIPS
O
O
O
O
I
I
TIPS
TIPS
TIPS-EBX
TIPS-EBX
67
67
Scheme 35. Direct C2-alkynylation of indoles via Pd(II)/Pd(IV) using alkynyl benzoiodoxolone 67.
Scheme 35.
35. Direct
Direct C2-alkynylation
C2-alkynylation of
of indoles
indoles via
via Pd(II)/Pd(IV)
Pd(II)/Pd(IV) using
Scheme
using alkynyl
alkynyl benzoiodoxolone
benzoiodoxolone 67.
67.
2.2.5.3. Trifluoromethylation
2.2.5.3. Trifluoromethylation
2.2.5.3.
Trifluoromethylation
Palladium-catalyzed approaches to arene trifluoromethylation are rare, largely because most
Palladium-catalyzed approaches
to
trifluoromethylation are
rare, largely
largely because
because most
most
Palladium-catalyzed
to 3arene
arene
trifluoromethylation
rare,
palladium
(II) species are approaches
inert to Ar-CF
bonding
forming reductiveare
elimination
[74–76]. Methods
palladium
(II)
species
are
inert
to
Ar-CF
3 bonding forming reductive elimination [74–76]. Methods
palladium
species are cycle
inert are
to Ar-CF
formingdue
reductive
[74–76].
Methods
3 bonding
involving a(II)
Pd(II)/Pd(IV)
an attractive
alternative
to moreelimination
facile reductive
eliminations
involving
a
Pd(II)/Pd(IV)
cycle
are
an
attractive
alternative
due
to
more
facile
reductive
eliminations
involving
Pd(II)/Pd(IV)
areUnfortunately,
an attractive alternative
to of
more
facile
reductive
eliminations
from highaoxidation
state cycle
Pd(IV).
a limiting due
factor
most
common
Pd(IV)
oxidants,
from high
high oxidation
oxidation state
state Pd(IV).
Pd(IV). Unfortunately,
a limiting
limiting factor
factor of
of most
most common
common Pd(IV)
oxidants,
from
Unfortunately,
a
Pd(IV)
oxidants,
including hypervalent iodine reagents, is the transfer of X-groups to the metal center that will
readily
including hypervalent
hypervalent iodine
iodine reagents,
reagents, is
is the
the transfer
transfer of
of X-groups
X-groups to
to the
metal
center
that
will
readily
including
the
metal
center
that
will
readily
outcompete a –CF3 group for reductive elimination. This problem was exemplified in studies
by
outcompete a –CF3 group for reductive elimination. This problem was exemplified in studies by
outcompete
a –CFthe
for reductive
elimination.
This problem
was exemplified
in studies
by
Sanford, wherein
synthesis
and stoichiometric
reactivity
of a Pd(IV)–CF
3 complex was
examined
3 group
Sanford, wherein the synthesis and stoichiometric reactivity of a Pd(IV)–CF3 complex was examined
Sanford,
wherein
the synthesis
and(Scheme
stoichiometric
reactivity
a Pd(IV)–CF
was examined
with a range
of common
oxidants
36) [77,78].
Upon of
oxidation
of complex
68, high
oxidation
3 complex
with a range of common oxidants (Scheme 36) [77,78]. Upon oxidation of complex 68, high oxidation
with
range of
common oxidants
(Scheme
36)two
[77,78].
Uponreductive
oxidationelimination
of complex pathways
68, high oxidation
state aPd(IV)
intermediate
69 could
undergo
possible
to form
state Pd(IV) intermediate 69 could undergo two possible reductive elimination pathways to form
state
intermediate
couldEmploying
undergo two
possible2 or
reductive
elimination pathways
to C–X
formbond
with
with Pd(IV)
an Ar–CF
3 or Ar–X69
bond.
PhI(OAc)
N-halosuccinimides
exclusive
with an Ar–CF3 or Ar–X bond. Employing PhI(OAc)2 or N-halosuccinimides
exclusive C–X bond
+
an
Ar–CF
or
Ar–X
bond.
Employing
PhI(OAc)
or
N-halosuccinimides
exclusive
C–X
bond
formation
formation3 was observed, in varying yields. Only
2 upon use of a “F ” source as an oxidant, the optimal
formation was observed, in varying yields. Only upon use+ of a “F+” source as an oxidant, the optimal
was
in varying
yields.
Onlyformation
upon use observed
of a “F ” in
source
an oxidant,
optimal being
beingobserved,
NFTPT (70),
was Ar–CF
3 bond
high as
yield
(71). Thisthe
landmark
study
being NFTPT (70), was Ar–CF3 bond formation observed in high yield (71). This landmark study
NFTPT
(70),feasibility
was Ar–CF
bond formation
observed
inahigh
yield
(71). This landmark
shows
the
shows the
of3Ar–CF
3 bond formation
via
Pd(IV)
intermediate,
howeverstudy
it also
exposes
shows the feasibility of Ar–CF3 bond formation
via a Pd(IV) intermediate, however it also exposes
+
feasibility
of
Ar–CF
bond
formation
via
a
Pd(IV)
intermediate,
however
it
also
exposes
the
limitations
the limitations of current
oxidants. Common “F ” sources are expensive relative to hypervalent iodine
3
the limitations of current oxidants.+ Common “F+” sources are expensive relative to hypervalent iodine
of
currentoroxidants.
Common “Fand
” sources
expensive
relative
to hypervalent
iodine
reagents
or
reagents
N-halosuccinimides
their useare
in catalytic
reaction
manifolds
of this type
is not
proven.
reagents or N-halosuccinimides and their use in catalytic reaction manifolds of this type is not proven.
N-halosuccinimides
and
their
use
in
catalytic
reaction
manifolds
of
this
type
is
not
proven.
Therefore,
Therefore, the identification of suitable oxidant/ligand combinations that will facilitate selective –CF3
Therefore, the identification of suitable oxidant/ligand combinations that will facilitate selective –CF3
the
identification
of suitable
oxidant/ligand
combinations
will
facilitate selective
reductive
elimination
from Pd(IV)
is of critical
importancethat
to the
advancement
of this–CF
area.
3 reductive
reductive elimination from Pd(IV) is of critical importance to the advancement of this area.
elimination from Pd(IV) is of critical importance to the advancement of this area.
Molecules 2017, 22, 780
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Me
TfO
Me
TfO
F
F
N
N
N
N
Pd II
Pd II
CF3
CF3
68
68
F
F
[Oxidant]–XY
[Oxidant]–XY
N
N
N
N
Pd IV
Pd IV
X
X
69
69
Me
N
F
CF3Me 70 N
70 F
CF
Y 3
Y
Me
Me
CF3
CF3
F
F 70%, 71
Aryl - CF 3
bond
Arylformation
- CF 3
bond formation
70%, 71
Traditional oxidants for Pd(IV) transfer ligands
that
will outcompete
for reductive
Traditional
oxidants–CF
for 3Pd(IV)
transferelimination
ligands
that will outcompete –CF3 for reductive elimination
X
X
PhI(OAc) 2
PhI(OAc) 2
NBS
NBS
NCS
NCS
Aryl - X
bond
formation
Aryl
-X
F
bond formation
F % (X= OAc)
20
20 % (X= OAc)
75 % (X= Br)
75 % (X= Br)
70 % (X= Cl)
70 % (X= Cl)
Scheme 36.
36. Isolation
study of
of –CF
–CF3 reductive
elmination from Pd(IV) complexes.
Scheme
Isolation and
and study
3 reductive elmination from Pd(IV) complexes.
Scheme 36. Isolation and study of –CF3 reductive elmination from Pd(IV) complexes.
In a significant report, the catalytic trifluoromethylation of indoles was reported by Liu, utilizing
In aa significant
significant report,
report, the
the catalytic
catalytic trifluoromethylation
trifluoromethylation of
indoles was
was reported
reported by
by Liu,
Liu, utilizing
utilizing
In
of indoles
TMSCF3 as the trifluoromethyl
source and PhI(OAc)2 as a stoichiometric
oxidant (Scheme
37) [79].
TMSCF
as
the
trifluoromethyl
source
and
PhI(OAc)
as
a
stoichiometric
oxidant
(Scheme
37) [79].
[79].
TMSCF
33 as the trifluoromethyl source and PhI(OAc)22 as a stoichiometric oxidant (Scheme 37)
The authors
propose a Pd(II)/Pd(IV) catalytic cycle, involving electrophilic palladation at Pd(II),
The authors
propose aa Pd(II)/Pd(IV)
catalytic cycle,
cycle, involving
involving electrophilic
electrophilic palladation
palladation at
at Pd(II),
Pd(II),
The
authors
followed
by propose
oxidation Pd(II)/Pd(IV)
by PhI(OAc)catalytic
2/TMSCF3 and reductive elimination. However, detailed
followed
by
oxidation
by
PhI(OAc)
/TMSCF
and
reductive
elimination.
However,
detailed
2 2/TMSCF33 and reductive elimination. However, detailed
followed
bysupport
oxidation
byprovided
PhI(OAc)
mechanistic
is not
and
this result is perhaps surprising given Sanford’s previous
mechanistic support
support is
is not
not provided
provided and
and this
this result is
surprising
given
previous
mechanistic
is perhaps
perhaps
surprising
given Sanford’s
Sanford’s
previous
reports detailing competitive –OAc vs. –CF3result
reductive
elimination
at Pd(IV)
[77,78]. Given
the
reports
detailing
competitive
–OAc
vs.
–CF
reductive
elimination
at
Pd(IV)
[77,78].
Given
the
complex
3
reports
competitive
–OAc employed,
vs. –CF3 reductive
elimination
at Pd(IV)
[77,78].
Given
the
complexdetailing
set of reaction
conditions
a more detailed
mechanistic
study
is required
to
set of reaction
conditions
employed,
a employed,
more detailed
mechanistic
study
is requiredstudy
to definitively
prove
complex
set
of
reaction
conditions
a
more
detailed
mechanistic
is
required
to
definitively prove the intermediacy of Pd(IV), and such a study could provide valuable insights for
the intermediacy
Pd(IV),
and suchof
a study
could
valuable
insights
for valuable
further development
definitively
proveofthe
Pd(IV),
and provide
such
study
could
provide
insights for
further development
ofintermediacy
Pd(IV) trifluoromethylation
withaPhI(OAc)
2 as an oxidant.
of
Pd(IV)
trifluoromethylation
with
PhI(OAc)
as
an
oxidant.
2
further development of Pd(IV) trifluoromethylation with PhI(OAc)2 as an oxidant.
R2
R2
R
R
H
N H
N R1
R1
Pd(OAc) 2 (10 mol%), 72
Pd(OAc)
72
(2 equiv.)
PhI(OAc)
2 (102 mol%),
PhI(OAc) 2 (2 equiv.)
CsF (4 equiv.)
CsF (43 (4
equiv.)
equiv)
TMSCF
(4 equiv)
TMSCF3(50
TEMPO
mol%)
TEMPO
CN,mol%)
rt
CH 3(50
CH 3CN, rt
R2
R2
R
R
CF3
N CF3
N R1
R1
33–75% yield
33–75% yield
O
O
N
N
N
N
O
O
72
72
Scheme 37. Catalytic trifluoromethylation of indoles with PhI(OAc)2 as the oxidant and TMSCF3 as
Scheme
PhI(OAc)22 as the oxidant and TMSCF
TMSCF33 as
37. Catalytic
trifluoromethylation of indoles with PhI(OAc)
the trifluoromethyl
source.
the trifluoromethyl source.
Due to the low reactivity towards reductive elimination, trifluoromethyl palladium complexes
Due
the low
reactivity
towards
reductive elimination,
trifluoromethyl
palladium
complexes
haveDue
beento
as reactivity
tools
to probe
mechanistic
and oxidation
states palladium
of
proposed
catalytic
toused
the low
towards
reductivedetails
elimination,
trifluoromethyl
complexes
have
been
used
as
tools
to
probe
mechanistic
details
and
oxidation
states
of
proposed
catalytic
intermediates.
There
is an to
ongoing
in details
the literature
whether Pd(IV)
monomeric
or
have
been used
as tools
probe discussion
mechanistic
and oxidation
states of
proposedspecies
catalytic
intermediates.
There
is are
an ongoing
discussionarising
in the literature
whether Pd(IV)
monomeric
species
or
Pd(III)–Pd(III)
dimers
the
intermediates
from
hypervalent
iodine
oxidation
of
a
Pd(II)
intermediates. There is an ongoing discussion in the literature whether Pd(IV) monomeric species
Pd(III)–Pd(III)
dimers2.3.2
are for
the further
intermediates
arising
fromhas
hypervalent
iodine
oxidation
a Pd(II)
species
(see Section
discussion).
Ritter
reported that
oxidation
of of
palladium
or
Pd(III)–Pd(III)
dimers are
the intermediates
arising
from hypervalent
iodine
oxidation
of a Pd(II)
species
(see
Section
2.3.2
for
further
discussion).
Ritter
has
reported
that
oxidation
of
palladium
complex(see
73 with
PhI(OAc)
2 and
PhICl
2 results in the
formation
of Pd(III)
[80].ofIn
contrast,
species
Section
2.3.2 for
further
discussion).
Ritter
has reported
that dimers
oxidation
palladium
complex
73 withthat
PhI(OAc)
2 and PhICl2 results in the formation of Pd(III) dimers [80]. In contrast,
Sanford
showed
oxidation
of
73
with
Togni’s
reagent
(74)
gave
rise
to
an
isolable
Pd(IV)
species
complex 73 with PhI(OAc)2 and PhICl2 results in the formation of Pd(III) dimers [80]. In contrast,
Sanford
showed
that
oxidation
of
73
with
Togni’s
reagent
(74)
gave
rise
to
an
isolable
Pd(IV)
species
(76) (Scheme
38) that
[81].oxidation
In this study,
reagent
gave the
of an
complex
76,Pd(IV)
as compared
Sanford
showed
of 73Togni’s
with Togni’s
reagent
(74)best
gaveyield
rise to
isolable
species
(76)
(Scheme
38) [81].“CF
In this
study, Togni’s
reagentstudy
gave between
the best yield
of complex
76, Yates,
as compared
+” sources.
to
other
electrophilic
3
A
subsequent
the
groups
of
Ritter,
Canty,
(76) (Scheme 38) [81]. In this study, Togni’s reagent gave the best yield of complex 76, as compared
to
other
electrophilic
“CF
3++
”
sources.
A
subsequent
study
between
the
groups
of
Ritter,
Yates,
Canty,
in other
collaboration
with “CF
Sanford,
showed that monomeric Pd(IV) complex 76 is likely formed through a
to
electrophilic
3 ” sources. A subsequent study between the groups of Ritter, Yates, Canty,
in
collaboration
with Sanford, showed that sequence,
monomeric Pd(IV) complex
76 is likely formed
a
two-step
oxidation/disproportionation
the intermediacy
of through
bimetallic
in
collaboration
with Sanford, showed that monomeric through
Pd(IV) complex
76 is likely formed
through a
two-step
oxidation/disproportionation
sequence,
through
the
intermediacy
of
bimetallic
intermediate
75 [82]. It is suggested that
formation
of the
bond that
occurs during
initial
two-step
oxidation/disproportionation
sequence,
through
thePd–Pd
intermediacy
of bimetallic
intermediate
intermediate
75
[82].
It
is
suggested
that
formation
of
the
Pd–Pd
bond
that
occurs
during
initial
oxidation
tosuggested
Pd(III) lowers
the activation
barrier
to bond
oxidation
en route
to 76.initial oxidation to Pd(III)
75
[82]. It is
that formation
of the
Pd–Pd
that occurs
during
oxidation to Pd(III) lowers the activation barrier to oxidation en route to 76.
lowers the activation barrier to oxidation en route to 76.
Molecules 2017, 22, 780
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24 of 54
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F 3C I
O
Me
Me
Molecules 2017, 22, 780
N
PdII O
O
24 of 54
N
F 3C I 74
O
Me
AcOH, CH 2Cl 2Me
Me
O Me
N II
Pd
OPdII O
Bimetallic Oxidation
74
N
Me
N
CF3
Pd III O
O
CF3IIIO
Pd
Pd III O
75O
CF 3
Disproportionation
Me
N
Me
OH 2
Pd IV
OAc
CF 3 OAc
OH
Pd IV 76 2
O Me
N
O
OAc
Bimetallic Oxidation
Me
Pd II O
Pd IIIO
OAc
N
SchemeN38. Evidence
for
intermediacy
of
bimetallic
Pd(III)
species
en
route
to
monomeric
Pd(IV)
75
73
76
Scheme 38. Evidence
for intermediacy of bimetallic Pd(III)
species en route to monomeric Pd(IV)
upon
N
O
73
AcOH, CH 2Cl 2
Disproportionation
Me
upon oxidation with Togni’s reagent.
oxidation with Togni’s reagent.
Scheme 38. Evidence for intermediacy of bimetallic Pd(III) species en route to monomeric Pd(IV)
upon oxidation with Togni’s reagent.
Miscellaneous
2.2.6.
2.2.6. Miscellaneous
Sanford
has reported an interesting transformation wherein enynes are converted to highly
2.2.6. Miscellaneous
Sanford has reported an interesting transformation wherein enynes are converted to
substituted cyclopropanes via a cyclization cascade employing Pd(OAc)2 and PhI(OAc)2 (Scheme 39)
Sanford hascyclopropanes
reported an interesting
transformation
wherein
enynes are
converted
to highly
highly substituted
via a cyclization
cascade
employing
Pd(OAc)
PhI(OAc)
2 and
[47]. substituted
In this case,
the high-oxidation
statecascade
of Pd(IV)
intermediate
(77) undergoes
nucleophilic2
cyclopropanes
via
a
cyclization
employing
Pd(OAc)
2 and PhI(OAc)2 (Scheme 39)
(Scheme 39) [47]. In this case, the high-oxidation state of Pd(IV) intermediate (77) undergoes
displacement
by an
internal
enol ether to generate
the cyclopropane
moiety
via an SN2-type
pathway,
[47]. In this
case,
the high-oxidation
state
of ether
Pd(IV)
(77)
undergoes
nucleophilic
nucleophilic
displacement
by an internal
enol
tointermediate
generate the
cyclopropane
moiety via an
analogous
to
Muniz’s
reports
on
Pd(IV)-mediated
amination
(see
Section
2.2.4.1).
Key
to
success
is
displacement by an internal enol ether to generate the cyclopropane moiety via an SN2-type pathway,
SN 2-type pathway, analogous to Muniz’s reports on Pd(IV)-mediated amination (see Section 2.2.4.1).
analogous
to Muniz’s
reports on
Pd(IV)-mediated
amination
(see Section
2.2.4.1).
to success
is
that the
rate of
intramolecular
cyclization
is faster
than that
of C–O
bondKey
forming
reductive
Key to success is that the rate of intramolecular cyclization is faster than that of C–O bond forming
that thefrom
rate 77
of and
intramolecular
cyclization
faster than
C–O bond forming reductive
elimination
trace amounts
of C–Oisproducts
(78)that
are of
observed.
reductive
elimination
77 and
trace amounts
of C–O(78)
products
(78) are observed.
elimination
from 77from
and trace
amounts
of C–O products
are observed.
R1
R
H
R
X
R
R1
Pd(OAc) 2 (5 mol%)
Pd(OAc)
2 (5-mol%)
PhI(OAc)
4 equiv.)
2 (1.1
H
X
PhI(OAc) 2 (1.1 - 4 equiv.)
O
Ph Ph
Ph
Ph
MeMe
OO
Pd(OAc)
Pd(OAc)
2 2
OO
H
AcO
X
78
Me
O
X
O
O
O
O
X
78O
O
O
Me H Ph
IV
AcO Pd
OAc
AcOIV
AcO Pd 77
AcO
OAc
77
X
X
O
O
O
Pd
O
O
X
H
Me X
O
PhI(OAc) 2
OAc
OAc
Pd II II
O
Me HPh
II
PdMe
OAc
O
O
O
O
AcO
Ph
II
Pd
H AcO
O
Ph
Me
PdII
O
Me H Ph
O
X
O
O
XO
Me
O
X
H H
X
Me
Me Ph O
Ph O
H
O
O
X = O, N
XX
Me H
Ph
AcO
Me H
O
X OO
X
X = O, N
44-79%
HH
Elimination Ph
R1
R1
H
44-79%
O
Me
Me
Competitive
Competitive
C–O Reductive
Elimination
C–O Reductive
H
R
O
X
O
O
O
OO
Ph
H
OO
X
PdII
Scheme
39. Cyclopropane
synthesis
Pd(II)/Pd(IV) catalysis
with
SO
N2-type displacement of Pd(IV).
OAc
Scheme
39. Cyclopropane
synthesis
viaviaPd(II)/Pd(IV)
catalysis
Xwith SN 2-type displacement of Pd(IV).
PhI(OAc) 2
2.3.
Palladium(III)
Scheme
39. Cyclopropane synthesis via Pd(II)/Pd(IV) catalysis with SN2-type displacement of Pd(IV).
2.3. Palladium(III)
2.3.1. Introduction
2.3.
Palladium(III)
2.3.1.
Introduction
In contrast to reactions with palladium in its 0, +1, +2, and +4 oxidation states, little is known
contrast
to reactions
with
palladium
its 0, +1,
+2,
+4 oxidation
states,
known
2.3.1.In
Introduction
about
the chemistry
of Pd(III)
dimers
or theirin
potential
role
in and
catalysis.
This has been
duelittle
to theislow
aboutstability
the chemistry
Pd(III) dimers
or their
rolecharacterization,
in catalysis. This
has
beenofdue
to the low
of these of
compounds,
hindering
theirpotential
isolation and
and
a lack
examples
In contrast to reactions with palladium in its 0, +1, +2, and +4 oxidation states, little is known
stability of these compounds, hindering their isolation and characterization, and a lack of examples
about the chemistry of Pd(III) dimers or their potential role in catalysis. This has been due to the low
stability of these compounds, hindering their isolation and characterization, and a lack of examples
Molecules 2017, 22, 780
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employing Pd(III) organometallic species in catalytic manifolds. Over the last 10 years, hypervalent
iodine
as as
excellent
oxidants
for the
of Pd(III)
dimersdimers
and these
iodine reagents
reagentshave
haveemerged
emerged
excellent
oxidants
for isolation
the isolation
of Pd(III)
andstudies
these
have
provided
key insights
the roleinto
thatthe
Pd(III)
play in carbo-heteroatom
bond
studies
have provided
keyinto
insights
roleintermediates
that Pd(III) could
intermediates
could play in carboforming
transformations.
In transformations.
this section we will
somewe
of will
the more
significant
this
heteroatom
bond forming
In highlight
this section
highlight
somestudies
of theinmore
area,
with
an
emphasis
on
those
that
relate
to
the
previously
discussed
Pd(II)/Pd(IV)
carbon-halogen
significant studies in this area, with an emphasis on those that relate to the previously discussed
and
carbon-oxygen
bond forming
Pd(II)/Pd(IV)
carbon-halogen
and reactions.
carbon-oxygen bond forming reactions.
2.3.2.
Complex Isolation
2.3.2. Complex
Isolation
Cotton
Cotton reported
reported the
the isolation
isolation and
and characterization
characterization of
of several
several dimeric
dimeric Pd(III)
Pd(III) species
species possessing
possessing
aa Pd–Pd
single
bond,
all
accessed
via
two,
one-electron
oxidations
of
dimeric
Pd(II)
precursors
Pd–Pd single bond, all accessed via two, one-electron oxidations of dimeric Pd(II) precursors with
with
PhICl
(Scheme 40)
40) [83,84].
[83,84]. In
In their
their initial
initial report,
PhICl22 (Scheme
report, cyclic
cyclic voltammetry
voltammetry measurements
measurements revealed
revealed that
that
Pd(II)
species
79,
with
a
bridging
hpp
(1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2–α]pyrimidine)
ligand,
Pd(II) species 79, with a bridging hpp (1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2–α]pyrimidine) ligand,
possessed
VV
and
anan
irreversible
oxidation
at +0.82
V hinting
at the
possessed aaquasi-reversible
quasi-reversibleoxidation
oxidationatat–0.12
–0.12
and
irreversible
oxidation
at +0.82
V hinting
at
low
stability
of
the
products.
Indeed,
while
they
were
able
to
achieve
oxidation
with
PhICl
,
products
2
the low stability of the products. Indeed, while they were able to achieve oxidation with
PhICl2,
were
isolated
in low
yield via
selection
crystals selection
amongst numerous
decomposition
products.
products
were
isolated
in manual
low yield
via ofmanual
of crystals
amongst numerous
A
subsequent
study
improved
on
the
oxidation
by
exploring
other
bridging
ligands
and
found
that
decomposition products. A subsequent study improved on the oxidation by exploring other bridging
while
it and
was found
possible
towhile
oxidize
Pd(II)
dimerstowith
a variety
electron-rich
and electron-deficient
ligands
that
it was
possible
oxidize
Pd(II)of
dimers
with a variety
of electron-rich
carboxylate
ligands
(80);
oxidation
became
inaccessible
upon
introduction
of
an
electron-deficient
and electron-deficient carboxylate ligands (80); oxidation became inaccessible upon introduction of
perfluorinated
aryl backbone
on the aryl
phosphine
ligand.
an electron-deficient
perfluorinated
backbone
on the phosphine ligand.
a. Cotton (1998)
N
N
N
N
Pd II
Pd II
79
Cl
N
N
N
PhICl 2
N
-PhI
N
N
N
N
N
Pd II
N
N
Pd II
N
N
N
N
(hpp)
N
Cl
N
=
b. Cotton (2006)
C
P
P
C
Cl
Pd II
Pd II
80
O
C
O
PhICl 2
P
O
-PhI
P
O
C
Pd III
Pd III
Cl
R
O
O
O
O = O
C
P
O
O
=
O
PPh 2
upon oxidation
oxidation with
with PhICl
PhICl22. (a) Use of an hpp bridging ligand
Scheme 40. Formation of Pd(III) dimers upon
bridging carboxylate
carboxylate and
and arylphosphine
arylphosphine ligands.
ligands.
(b) Use of bridging
Ritter has conducted extensive studies on the potential role that bimetallic Pd(III) dimers could
Ritter has conducted extensive studies on the potential role that bimetallic Pd(III) dimers could
play in what had been widely proposed to be Pd(II)/Pd(IV) catalytic cycles (Scheme 41) [80,82,85].
play in what had been widely proposed to be Pd(II)/Pd(IV) catalytic cycles (Scheme 41) [80,82,85].
The first definitive report for the presence of Pd(III) intermediates was in 2009. The oxidation of a
The first definitive report for the presence of Pd(III) intermediates was in 2009. The oxidation of a
dimeric Pd(II) complex (81) was examined employing oxidants common to Pd(II)/Pd(IV) C–X bond
dimeric Pd(II) complex (81) was examined employing oxidants common to Pd(II)/Pd(IV) C–X bond
forming reactions, including PhI(OAc)2, PhICl2, or N-halosuccinimides. Oxidation of 81 with PhICl2
forming reactions, including PhI(OAc)2 , PhICl2 , or N-halosuccinimides. Oxidation of 81 with PhICl2
gave rise to Pd(III) intermediate 82, which was characterized by X-ray crystallography. The Pd–Pd
gave rise to Pd(III) intermediate 82, which was characterized by X-ray crystallography. The Pd–Pd
bond length in 82 is 2.84 Å, which strongly suggests a metal-metal single bond and bond order of
bond length in 82 is 2.84 Å, which strongly suggests a metal-metal single bond and bond order
zero. Therefore, in a net two-electron oxidation, PhICl2 oxidizes each palladium center by one electron
of zero. Therefore, in a net two-electron oxidation, PhICl2 oxidizes each palladium center by one
(d8 -> d7), which results in formation of a metal-metal single bond. Detailed mechanistic and
electron (d8 -> d7 ), which results in formation of a metal-metal single bond. Detailed mechanistic and
computational studies support that 82 is then able to undergo a concerted reductive elimination event
computational studies support that 82 is then able to undergo a concerted reductive elimination event
wherein both components of the new C–X bond arise from a single palladium center. A subsequent
wherein both components of the new C–X bond arise from a single palladium center. A subsequent
report from Ritter provides additional evidence that a Pd (III) dimer is the kinetically competent
report from Ritter provides additional evidence that a Pd (III) dimer is the kinetically competent
species in the acetoxylation of 2-phenylpyridine with Pd(OAc)2/PhI(OAc)2 [85].
species in the acetoxylation of 2-phenylpyridine with Pd(OAc)2 /PhI(OAc)2 [85].
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PhICl 2
2
N
N
Pd(OAc)L
- 2L
+ 2L
PhI
N
Pd II O
O
O
Pd II O
N
81
Bimetallic
Oxidative
Addition
Me
Me
N
Cl
Pd III O
O
O
Pd IIIO
Cl
Fast
Equilibrium
Cl
N
Me
Me
N
82
Pd
O
O
O
Pd O
L
Me
Me
Cl
Bimetallic
Reductive
Elimination
HCl
Cl
H
N
N
Scheme41.
41.First
Firstevidence
evidencefor
for the
the role
role of
of bimetallic
Scheme
bimetallicPd(III)
Pd(III)dimers
dimersinincatalysis.
catalysis.
Together, these reports are the first to show the catalytic competence of Pd(III) dimers in C–X
Together,
reports
thefuel
first
to show
the catalytic
competence
of Pd(III)
dimers
in C–X
bond
formingthese
reactions
andare
could
further
investigations
in the
area of bimetallic
Pd(III)
catalysis.
bond
forming
reactions
and
could
fuel
further
investigations
in
the
area
of
bimetallic
Pd(III)
catalysis.
Furthermore it supports the consideration of Pd(III) dimers along Pd(II)/Pd(IV) catalytic cycles
Furthermore
it supports iodine
the consideration
of Pd(III) dimers along Pd(II)/Pd(IV) catalytic cycles
employing hypervalent
oxidants.
employing hypervalent iodine oxidants.
2.3.3. Conclusions
2.3.3. Conclusions
High valent palladium chemistry represents one of the most well developed areas of high
High valent
palladium
chemistry
represents
of theofmost
well
developed
areas of high
oxidation
state metal
catalysis.
Advancements
in theone
formation
a wide
range
of carbon-heteroatom
oxidation
state metalC–O,
catalysis.
the formation
a wide
rangehave
of carbon-heteroatom
bonds including
C–X, Advancements
C–N, as well asinC–C
bonds via of
this
manifold
been reported.
bonds
including
C–X, C–N, as
well
as C–C
viawidely
this manifold
been reported.
PhI(OAc)2
PhI(OAc)
2 andC–O,
diaryliodonium
salts
have
beenbonds
the most
appliedhave
hypervalent
iodine reagents
indiaryliodonium
catalytic methodsalts
development
PhIClwidely
2 has been
successfully
used iodine
for high
valent in
complex
and
have beenand
the most
applied
hypervalent
reagents
catalytic
isolation.
Detailed mechanistic
have
revealed used
clear for
evidence
for Pd(II)/Pd(IV)
redox couples
method
development
and PhICl2 studies
has been
successfully
high valent
complex isolation.
Detailed
in these processes,
however
the role
Pd(III)-dimers
along the catalytic
cycles is in
becoming
more
mechanistic
studies have
revealed
clearofevidence
for Pd(II)/Pd(IV)
redox couples
these processes,
evident.
Current
limitations
remain
in
the
reductive
elimination
of
challenging
groups
such
as
however the role of Pd(III)-dimers along the catalytic cycles is becoming more evident. Current
fluoride remain
or trifluoromethyl
groups,
and development
of oxidants
not possess
competitive
limitations
in the reductive
elimination
of challenging
groups that
suchdo
as fluoride
or trifluoromethyl
ligands
for
reductive
elimination
would
significantly
contribute
to
this
area.
groups, and development of oxidants that do not possess competitive ligands for reductive elimination
would significantly contribute to this area.
3. Platinum
3. Platinum
Platinum has played a pivotal role in the evolution of oxidative couplings. Arguably, the “Shilov
system”
was has
the first
significant
example
intermolecular
C–H
functionalization,
wherein
the
Platinum
played
a pivotal
role ofinanthe
evolution of
oxidative
couplings.
Arguably,
oxidation of alkanes to a mixture alcohols and alkyl chlorides was mediated by an aqueous solution
the “Shilov system” was the first significant example of an intermolecular C–H functionalization,
of [PtCl42−] and [PtCl62−] (Scheme 42a) [86]. Since this seminal discovery, extensive studies have been
wherein the oxidation of alkanes to a mixture alcohols and alkyl chlorides was mediated by an aqueous
conducted on the Pt(II)/Pt(IV) redox couple, as well as the potential formation of Pt(III) dimeric
solution of [PtCl4 2− ] and [PtCl6 2− ] (Scheme 42a) [86]. Since this seminal discovery, extensive studies
species. Oxidation of square planar Pt(II) to octahedral Pt(IV) is significantly more facile than
have been conducted on the Pt(II)/Pt(IV) redox couple,
as well as the potential formation of Pt(III)
palladium (standard reduction potentials of [PtCl62−] and [PdCl62−] are +0.68 V and +1.29 V,
dimeric
species. Oxidation of square planar Pt(II) to octahedral Pt(IV) is significantly more facile
respectively) [86], however, Pt(II)/Pt(IV) mediated oxidative couplings are comparatively rare. This
2−
2− ] are +0.68 V and +1.29 V,
than
palladium
(standard higher
reduction
potentials
of [PtCl
6 ] and
6 relative
is due to the significantly
barrier
to reductive
elimination
for[PdCl
Pt(IV)
to Pd(IV) [87]. The
respectively)
[86], however,
mediated
oxidative
couplings
comparatively
rare.for
This
enhanced stability
of Pt(IV)Pt(II)/Pt(IV)
complexes has
been exploited
in their
use asare
isolable
model systems
is due
to theofsignificantly
barrierredox
to reductive
for Pt(IV)
relative
to Pd(IV)
[87].
the study
more elusivehigher
Pd(II)/Pd(IV)
couples elimination
[88]. Mechanistic
insights
provided
by these
The
enhanced
stability
of
Pt(IV)
complexes
has
been
exploited
in
their
use
as
isolable
model
systems
studies have been recently reviewed [88,89] and this section will cover recent advancements in Pt(IV)
forchemistry
the studyas
ofthey
morerelate
elusive
Pd(II)/Pd(IV)
redox
couples [88]. Mechanistic insights provided by these
to hypervalent
iodine
reagents.
studies have been recently reviewed [88,89] and this section will cover recent advancements in Pt(IV)
chemistry as they relate to hypervalent iodine reagents.
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a. Shilov (1976 )
Cl
a. Shilov (1976 )
H 2Pt IVCl6
H 2Pt IVCl6
a. TFA/H2O
H 3N
a. NH
TFA/H
b.
3 2O
HCl
3N
NH 4
Cl Cl
Pt IV
Cl
Pt IV
Cl
NH 4
b. NH 3
Cl
Stoichiometric C-H activation at Pt(IV)
Cl
Stoichiometric C-H activation at Pt(IV)
b. Modern studies on Pt(IV)
[O] = PhI(OAc) 2, PhICl 2, Ar2I[X], [(Py) 2IPh]2OTf –
as astudies
model system
for Pd(IV)
b. Use
Modern
on Pt(IV)
[O] = PhI(OAc) 2, PhICl 2, Ar2I[X], [(Py) 2IPh]2OTf –
R
R
Use as a model system for Pd(IV)
- common in catalysis
R
R
R - relatively unreactive
R IV R
R
Pd
PtIV
- unstable
- relatively stable
common in to
catalysis
unreactive
R - relatively
R
R
RR
--challenging
isolate RR
- often isolable
IV
IV
Pd
Pt
- unstable
- relatively stable
R
R
R
R
R
- challenging to isolate R
- often isolable
R
R
Development of Pt(II)/Pt(IV) C–H activation
Development
C–Hof Pt(II)/Pt(IV) C–H activation
[O]
activation
C–H
PtX 2
R Pt II X
[O]
–HX
activation
PtX 2
R Pt II X
–HX
C–X reductive elimination
X
IV
Pt
X
X
R X
Pt IV
X
R
X
C–X reductive elimination
has displayed divergent
reactivity and selectivity to Pd(IV)
has displayed divergent
R X reactivity and selectivity to Pd(IV)
R X
Scheme
StoichiometricC–H
C–Hfunctionalization
functionalizationofofnaphthalene
naphthaleneby
byShilov;
Shilov;(b)
(b)General
Generalscheme
schemefor
Scheme
42.42.
(a)(a)
Stoichiometric
for
modern
applications
Pt(II)/Pt(IV)
redox
couples
with
hypervalent
iodine
oxidants.
Scheme
42. (a) Stoichiometric
C–H
functionalization
of naphthalene
by Shilov;
(b) General scheme
modern
applications
Pt(II)/Pt(IV)
redox
couples with hypervalent
iodine
oxidants.
for modern applications Pt(II)/Pt(IV) redox couples with hypervalent iodine oxidants.
3.1. Complex Isolation
3.1. Complex Isolation
3.1. Complex Isolation
Canty has conducted many of the seminal reports on the isolation of various Pt(IV) and Pd(IV)
Canty has conducted many of the seminal reports on the isolation of various Pt(IV) and Pd(IV)
complexes
via conducted
oxidation many
with both
and reports
alkynyliodonium
saltsof(Scheme
43) [63–66].
The
Canty has
of thearyl
seminal
on the isolation
various Pt(IV)
and Pd(IV)
complexes
via
oxidation
with
both aryl
and alkynyliodonium
saltsa (Scheme
43)
[63–66].
The iodonium
iodonium
salts
were
able
to
cleanly
oxidize
Pt(II)
complexes
with
variety
of
ligand
scaffolds,
giving
complexes via oxidation with both aryl and alkynyliodonium salts (Scheme 43) [63–66]. The
salts
were
able
cleanly
oxidize
Pt(II)
complexes
with awith
variety
of ligand
scaffolds,
giving
rise
rise
to varying
degrees
of cis/trans
isomers
(83-cis
83-trans),
at
low
temperature.
Forscaffolds,
characterization
iodonium
saltsto
were
able
to
cleanly
oxidize
Pt(II)or
complexes
a variety
of ligand
giving
to purposes
varying
degrees
of
cis/trans
isomers
(83-cis
or
83-trans),
at
low
temperature.
For
characterization
thesedegrees
complexes
were isomers
then treated
NaI resulting
in triflate displacement,
and a
rise to varying
of cis/trans
(83-ciswith
or 83-trans),
at low temperature.
For characterization
purposes
these
were
thenthen
treated
with
NaI
resulting
triflate
displacement,
and a summary
summary
of complexes
the complexes
complexes
synthesized
via
thiswith
approach
is in
provided
below displacement,
(compounds
84–88).
purposes
these
were
treated
NaI resulting
in triflate
and a
of Throughout
the complexes
via this
approach
is approach
provided
84–88). complexes
Throughout
reports, Canty
notes
the
higher
stabilityisbelow
of
the(compounds
resultant
summary
of these
thesynthesized
complexes
synthesized
via this
provided
below platinum
(compounds
84–88).
these
reports,
Canty
the higher
stability
ofhigher
the
resultant
platinum
complexes
relative
to
palladium,
relative
to palladium,
facilitating
and
structural
characterization
that was
not possible
with
Throughout
thesenotes
reports,
Cantyisolation
notes
the
stability
of the resultant
platinum
complexes
facilitating
and
structural
characterization
thatcharacterization
was
notanalogous
possible
with
the possible
corresponding
the
corresponding
palladium
species.
For a further
discussion
of the
components
relative
toisolation
palladium,
facilitating
isolation
and structural
thatpalladium
was not
with
to
studies,
seea Section
2.2.5.1.
palladium
species.
For
furtherspecies.
discussion
the analogous
components
to Canty’s
studies,
theCanty’s
corresponding
palladium
For aof
further
discussionpalladium
of the analogous
palladium
components
Canty’s2.2.5.1.
studies, see Section 2.2.5.1.
seetoSection
R
R
R
R
[IAr 2]OTf
or
[IAr 2]OTf
[PhIC orCR]OTf
PtII
–60 °C
[PhIC
CR]OTf
PtII
–60 °C
C CR
R 2R 2 = –Ph,
C CR
R 2IV
Pt
OTf
PtIV
83-trans
OTf
83-trans
N
PhIV
Pt
N
Pt
I IV N
84 R = Ph, Me
I
84 R = Ph, Me
Pt
I IV
85
I
85
N
PhIV
Pt
R
R2
or R
R2
or
CR
Ph
Ph
R
R
R
R
R
R
R
R
R 2 = –Ph,
Me
Me
Me
Me
CR
Pt IV
Pt
I IV
86
I
86
R
Pt
R IV
OTf
PtIV
83-cis
OTf
83-cis
N
N
R2
NaI
25
°C
NaI
25 °C
R
R
R
R
R 2IV
Pt
I IV
Pt
I
CO 2R
NMe 2
CO 2R
IV I
PtNMe
2
NMe
Pt2IV I
87 C
NMe 2
CR
87 C
CR
R
R
R2
or R
R2
or
Pt
R IV
I IV
Pt
I
CR
CR
Me
Pt IV
Me
Me
Pt
I IV
Me 88
I
88
Me 2
P
Me 2
P
P
Me 2
P
Me 2
Scheme 43. Characterization of Pt(IV) upon oxidation with diaryl and alkynyliodonium salts.
Scheme
Characterizationof
ofPt(IV)
Pt(IV) upon
upon oxidation
oxidation with
salts.
Scheme
43.43.Characterization
withdiaryl
diaryland
andalkynyliodonium
alkynyliodonium
salts.
In 2005, Sanford reported the oxidation of benzo[h]quinoline supported Pt(II)acac complex 89
2 in an reported
effort to the
gainoxidation
mechanistic
insights into the supported
analogous Pt(II)acac
Pd(II)/Pd(IV)
system
with In
PhI(OAc)
2005, Sanford
of benzo[h]quinoline
complex
89
In 2005, Sanford reported the oxidation of benzo[h]quinoline supported Pt(II)acac complex 89
(Scheme
44) [90].
it was
found that
solvent
had
pronounced
effect on product
2 in Interestingly,
an effort to gain
mechanistic
insights
into
thea analogous
Pd(II)/Pd(IV)
system
with PhI(OAc)
with
PhI(OAc)2 in
an effort
to gaindimer
mechanistic
insights while
into the analogous
Pd(II)/Pd(IV)
system
distribution.
AcOH,
Pt(III)–Pt(III)
90 wasthat
obtained,
of Pt(IV)
alkoxides
(91,
92)
(Scheme 44)In
[90].
Interestingly,
it was found
solvent hada mixture
a pronounced
effect
on product
(Scheme
44)
[90].
Interestingly,
it
was
found
that
solvent
had
a
pronounced
effect
on
product
were
obtained
in the Pt(III)–Pt(III)
alcoholic solvents,
with
dependent
the steric
bulkalkoxides
of the alcohol.
distribution.
In AcOH,
dimer 90
wasratios
obtained,
while a on
mixture
of Pt(IV)
(91, 92)
distribution.
In AcOH,
Pt(III)–Pt(III)
dimer
90 ratios
wasligands,
obtained,
a mixture
of Pt(IV)
alkoxides
Alcoholic
solvents
are alcoholic
not
able tosolvents,
serve
as with
bridging
thuswhile
resulting
in preferential
formation
were obtained
in the
dependent
on the
steric
bulk
of the
alcohol.
(91,Alcoholic
92) were
obtained
solvents,
ratios
dependent
onpreferential
the steric formation
bulk of the
solvents
are in
notthe
ablealcoholic
to serve as
bridgingwith
ligands,
thus
resulting in
Molecules 2017, 22, 780
28 of 54
Molecules 2017, 22, 780
28 of 54
alcohol. Alcoholic solvents are not able to serve as bridging ligands, thus resulting in preferential
of the monomeric
species (91,
92) (91,
and92)
such
were were
hypothesized
to be
to
formation
of the monomeric
species
andcomplexes
such complexes
hypothesized
to analogous
be analogous
intermediates
in
Pd(II)/Pd(IV)
C–H
oxygenations.
In
contrast,
isolation
of
Pt(III)–Pt(III)
90
was
to intermediates in Pd(II)/Pd(IV) C–H oxygenations. In contrast, isolation of Pt(III)–Pt(III) 90 was
surprising asasthese
these
intermediates
not invoked
been invoked
in Pd(II)/Pd(IV)-catalyzed
surprising
intermediates
had had
not been
in Pd(II)/Pd(IV)-catalyzed
processes,processes,
however
however subsequent
studies
from
Ritter, and
Sanford,
others
have
theofviability
of Pd(III)
subsequent
studies from
Ritter,
Sanford,
othersand
have
shown
theshown
viability
Pd(III) dimers
in
dimers
in
these
processes
(see
Section
2.3.1.2).
Only
0.5
equivalents
of
PhI(OAc)
2
were
needed
for
these processes (see Section 2.3). Only 0.5 equivalents of PhI(OAc)2 were needed for formation of
formation
of either the
monomeric
or bimetallic
providing
evidenceproceed
that both
either
the monomeric
or bimetallic
species,
providing species,
strong evidence
thatstrong
both pathways
via
pathways
proceed
via
two-electron
oxidation.
two-electron oxidation.
Me
O
N
PtII
89
O
O
Me
Me
0.5 equiv.
PhI(OAc) 2
N
N
AcOH
PtIII
PtIII
O
O
O
O
Me
Me
Me
O
0.5 equiv.
PhI(OAc) 2
ROH
90 Me
Me
OR
N
PtIV
OR
91
O
O
Me
Me
Me
O
N
PtIV
OAc
92
O
OR
ROH
Ratio (91:92)
MeOH
EtOH
iPrOH
2.0:1.0
1.6:1.0
0.4:1.0
Scheme 44.
44. Benzo[h]quinoline
Pt(II) oxidation
oxidation studies.
studies. Effect
of solvent
solvent on
on oxidation
oxidation product
product ratios.
ratios.
Scheme
Benzo[h]quinoline Pt(II)
Effect of
A subsequent study by Sanford examined the oxidation of 2-phenylpyridine Pt(II) complex 93 with
A subsequent study by Sanford examined the oxidation of 2-phenylpyridine Pt(II) complex 93
PhICl2, which led to a mixture of cis and trans Pt(IV) complexes (94-cis 94-trans, Scheme 45a) [91]. This
with PhICl2 , which led to a mixture of cis and trans Pt(IV) complexes (94-cis 94-trans, Scheme 45a) [91].
was particularly interesting as the analogous Pd(II) complex has been found to give exclusive
This was particularly interesting as the analogous Pd(II) complex has been found to give exclusive
formation of the cis isomer (95) upon oxidation with PhICl2. Pt(II) complex 93 was also subject to a
formation of the cis isomer (95) upon oxidation with PhICl2 . Pt(II) complex 93 was also subject to
delicate interplay between Pt(IV) and Pt(III)–Pt(III) dimer formation upon oxidation, similar to their
a delicate interplay between Pt(IV) and Pt(III)–Pt(III) dimer formation upon oxidation, similar to
previous report [90], however in this case product ratios were contingent on choice of external
their previous report [90], however in this case product ratios were contingent on choice of external
oxidant. Whereas PhICl2 gave exclusively Pd(IV) monomers, altering the oxidant to NCS provided a
oxidant. Whereas PhICl2 gave exclusively Pd(IV) monomers, altering the oxidant to NCS provided a
Pt(III)–Pt(III) dimer as the major product (not shown). Rourke and co-workers showed that treatment
Pt(III)–Pt(III) dimer as the major product (not shown). Rourke and co-workers showed that treatment
of Pt(II) complex 96 with PhICl2 resulted in two-electron oxidation with concomitant C–H activation
of Pt(II) complex 96 with PhICl2 resulted in two-electron oxidation with concomitant C–H activation
to provide Pt(IV) dichloride 98 even at temperatures as low as −40 °C (Scheme 46b) [92]. This result
to provide Pt(IV) dichloride 98 even at temperatures as low as −40 ◦ C (Scheme 46b) [92]. This
is notable as previous studies employing other oxidants (peroxides and molecular oxygen) produced
result is notable as previous studies employing other oxidants (peroxides and molecular oxygen)
complex mixtures. It is proposed that oxidation proceeds via a five-coordinate, cationic Pt(IV)
produced complex mixtures. It is proposed that oxidation proceeds via a five-coordinate, cationic
intermediate (97) that is highly active towards arene functionalization.
Pt(IV) intermediate (97) that is highly active towards arene functionalization.
Building on Ritter’s use of poly(cationic) λ3-iodanes in high oxidation state nickel and
Building on Ritter’s use of poly(cationic) λ3 -iodanes in high oxidation state nickel and
palladium-mediated fluorination (see Sections 2.2.3.1 and 5.3), Dutton investigated the potential of
palladium-mediated
fluorination (see Section 2.2.3.1 and Section 5.3), Dutton investigated the potential
poly(cationic) λ3-iodanes to access a range of dicationic Pd(IV) and Pt(IV) complexes through the
of poly(cationic) λ3 -iodanes to access a range of dicationic Pd(IV) and Pt(IV) complexes through
delivery of neutral heterocyclic ligands to the metal center (Scheme 46) [93]. They found that 2the delivery of neutral heterocyclic ligands to the metal center (Scheme 46) [93]. They found
phenylpyridine Pt(II) complex 93 could be cleanly oxidized to Pt(IV) complex 100 with a DMAPthat 2-phenylpyridine Pt(II)
complex 93 could be cleanly oxidized to Pt(IV) complex 100 with a
derived poly(cationic) λ3-iodane
99 (Scheme 46a). However, oxidation of dimethyl Pt(II) 101 led to a
DMAP-derived poly(cationic) λ3 -iodane 99 (Scheme 46a). However, oxidation of dimethyl Pt(II) 101 led
less defined product distribution (Scheme 46b), possibly arising from oxidative disproportionation.
to a less defined product distribution (Scheme 46b), possibly arising from oxidative disproportionation.
This reactivity has been documented in similar Pt(II)/Pt(IV) redox couples, however the intermediacy
This reactivity has been documented in similar Pt(II)/Pt(IV) redox couples, however the intermediacy
of Pt(III) intermediates cannot be ruled out in this case [94]. These oxidations were also performed on
of Pt(III) intermediates cannot be ruled out in this case [94]. These oxidations were also performed on
the analogous palladium complexes, which were found to be too unstable for isolation and
the analogous palladium complexes, which were found to be too unstable for isolation and underwent
underwent rapid disproportionation. While the Pt(IV) species 100 and 102 were isolable, it is notable
that they are considerably less stable than complexes possessing anionic chloride or acetate ligands,
and similar stability trends were observed for the palladium complexes. While this is detrimental in
Molecules 2017, 22, 780
29 of 54
rapid disproportionation. While the Pt(IV) species 100 and 102 were isolable, it is notable that they are
considerably less stable than complexes possessing anionic chloride or acetate ligands, and similar
Molecules
2017,were
22, 780observed for the palladium complexes. While this is detrimental in the29
of 54
stability
trends
context
of
Molecules 2017, 22, 780
29 of 54
complex isolation, it could be adventitious for enhancing the reactivity of both high-oxidation state
the context of complex isolation, it could be adventitious for enhancing the reactivity of both highpalladium
andstate
platinum
species
catalysis.
the
context
of complex
isolation,
it couldspecies
be adventitious
for enhancing the reactivity of both highoxidation
palladium
and in
platinum
in catalysis.
oxidation state palladium and platinum species in catalysis.
a. Sanford (2008)
a. Sanford (2008)
N
N
PtII
PtII
N
N
PhICl 2
PhICl 2
N
N
93
93
Cl
Cl
Pt IV
Pt IV
N
N
Cl
Cl
Cl
Cl IV
Pt
Pt IV
Cl
Cl
N
N
94-cis (64%)
94-cis (64%)
Cl
Cl
Cl
Pd IV
Cl
Pd IV
N
N
N
N
N
N
95
95
Pd(IV)- cis
formed
exclusively
Pd(IV)cis
formed exclusively
94-trans (29%)
94-trans (29%)
b. Rourke (2008)
b. Rourke (2008)
N
N
F
F
F
F
Cl
PtII Cl
PtII N
N
PhICl 2
PhICl 2
96
96
N
N
Cl
PtIV Cl
IV
Pt Cl
Cl
N
N
F
F
F
Arene C–H
Activation
Arene
C–H
Activation
84%
84%
N
N
Cl
Pt IV Cl
IV
Pt
Cl
Cl
N
F
F
F
N
97
97 intermediate
proposed
98
98
proposed intermediate
Scheme
(a) Oxidation
of 2-phenylpryidine
Pt(II)
complex
with PhICl
2. Divergent complex
Scheme
45. (a)45.
Oxidation
of 2-phenylpryidine
Pt(II) Pt(II)
complex
with PhICl
. Divergent
complex geometry
Scheme
(a)Pd(II);
Oxidation
of 2-phenylpryidine
complex
with 2PhICl
2. Divergent complex
geometry45.
from
(b) Pt(II)
oxidation with PhICl
2 resulting in arene C–H activation.
from geometry
Pd(II); (b)from
Pt(II)
oxidation
with
PhICl
resulting
in
arene
C–H
activation.
2
Pd(II); (b) Pt(II) oxidation with PhICl2 resulting in arene C–H activation.
a.
a.
NMe 2
NMe 2
N
N
Pt II
Pt II
N
N
+
+
93
93
N
NI
I
N
N
2 OTf –
2 OTf –
2
2
NMe 2
NMe 2
N
N
- PhI
- PhI
NMe 2
NMe 2
99
99
N
N
Pt IV
Pt IV
N
N
NMe 2
NMe 2
N
N
100
100
b.
b.
NMe 2
NMe 2
N
N
Pt II
Pt II
101
101
Me
Me
Me
Me
+
+
99
99
N
N
Me
Pt IV Me
Me
IV
Pt
Me Me
102 Me
102
N
N
N
N
N
N
PtII
PtII
103
103
Pt II
Pt II
N
N
Me
Me
NMe 2
NMe 2
104
104
N
N
N
N
NMe 2
NMe 2
2
2
NMe 2
NMe 2
Products Detected
by Mass
Products
Detected
Spectrometry
by Mass
Spectrometry
Scheme 46. Dicationic [PhI(4-DMAP)2][OTf] mediated oxidation of (a) 2-Phenylpyridine Pt(II) complex
Scheme 46. Dicationic [PhI(4-DMAP)2][OTf] mediated oxidation of (a) 2-Phenylpyridine Pt(II) complex
93; (b)
Pt(II)
complex 101.2 ][OTf] mediated oxidation of (a) 2-Phenylpyridine Pt(II) complex
Scheme
46. Dimethyl
Dicationic
[PhI(4-DMAP)
93; (b) Dimethyl Pt(II) complex 101.
93; (b) Dimethyl Pt(II) complex 101.
3.2. Catalytic Applications
3.2. Catalytic Applications
While
platinum is most commonly employed as a model system, recent advancements have shown
3.2. Catalytic
Applications
While platinum
most commonly
employed
as a model
recent
advancements have
shown
its viability
in catalyticismanifolds.
Particularly
interesting
is the system,
finding that
platinum-catalyzed
processes
its
viability
in
catalytic
manifolds.
Particularly
interesting
is
the
finding
that
platinum-catalyzed
processes
While
platinum
is
most
commonly
employed
as
a
model
system,
recent
advancements
have
often display divergent reactivity and selectivity to those mediated by palladium.
often
display
divergent
reactivity
and
selectivity
to
those
mediated
by
palladium.
shown
its Suna
viability
in
catalytic
manifolds.
Particularly
interesting
is
the
finding
that
platinum-catalyzed
reported that PtCl2 with PhI(OAc)2 cleanly acetoxylated the C-3 position on various indoles
Suna
reported
that
PtCl2 2was
with
PhI(OAc)
2 cleanly acetoxylated the C-3 position on various indoles
processes
often
display
divergent
reactivity
and
selectivity
those mediated
palladium.
(Scheme
47)
[95]. Pd(OAc)
also
a competent
catalyst,tohowever
PtCl2 wasbyfound
to be more
(Scheme 47) [95]. Pd(OAc)2 was also a competent catalyst, however PtCl2 was found to be more
Molecules 2017, 22, 780
30 of 54
Suna reported that PtCl2 with PhI(OAc)2 cleanly acetoxylated the C-3 position on various
Molecules 2017, 22, 780
30 of 54
indoles (Scheme 47) [95]. Pd(OAc)2 was also a competent catalyst, however PtCl2 was found to
Molecules
2017, 22, 780
30 of 54
be
more giving
efficient,
giving
cleanerand
reactions
and higher
isolated
yields. Other
oxidants
efficient,
cleaner
reactions
higher isolated
yields.
Other oxidants
including
K2S2O8,including
m-CPBA,
K
S
O
,
m-CPBA,
t-BuOOH,
and
Cu(OAc)
were
all
completely
ineffective
(0%
conversion)
and
Mg
2 2 8
2
t-BuOOH,
and Cu(OAc)2 were all completely
ineffective (0% conversion) and Mg peroxyphthalate
efficient, givinggave
cleaner
reactions
and higher
isolated yields.
Other
oxidantsoxidation
including to
K2the
S2O8active
, m-CPBA,
peroxyphthalate
a
complex
mixture
of
products.
While
not
reported,
Pt(IV)
gave a complex mixture of products. While not reported, oxidation to the active Pt(IV) species would
t-BuOOH,
Cu(OAc)
2 were all completely ineffective (0% conversion) and Mg peroxyphthalate
species
wouldand
likely
proceed
through similar
intermediates
shown
likely
proceed
through
intermediates
to thosesimilar
showntointhose
Scheme
43. in Scheme 43.
gave a complex mixture of products. While not reported, oxidation to the active Pt(IV) species would
likely proceed through intermediates similar to those shown in Scheme 43.
OAc
R3
R3
N
RN1
R2
R2
5 mol% PtCl 2,
PhI(OAc) 2
5 mol% PtCl 2,
AcOH
PhI(OAc)
2
AcOH
R3
R3
R
R1 = CO 2R, Me, Ar
R 2 = Me, Ar
RR1 ==CO
R, Me, Ar
3 Br,2 I, OMe, CN, NO 2
R 2 = Me, Ar
R 3 = Br, I, OMe, CN, NO 2
OAc
R2
N
R2
NR1
R
1
1
Scheme
47.PtCl
PtCl22/PhI(OAc)
/PhI(OAc)22 mediated
Scheme
47.
mediated C-3
C-3 acetoxylation
acetoxylation of
of indoles.
indoles.
Scheme 47. PtCl2/PhI(OAc)2 mediated C-3 acetoxylation of indoles.
In 2013, Sanford provided the first example of an intermolecular C(sp2)–H arylation enabled by
In 2013, Sanford provided the first example of an intermolecular C(sp22 )–H arylation enabled by
In 2013,manifold
Sanford provided
the first
of an intermolecular
C(spa)–H
arylation
enabled
a Pt(II)/Pt(IV)
(Scheme 48a)
[96].example
The reaction
was found to have
much
broader
scope by
than
a Pt(II)/Pt(IV) manifold (Scheme 48a) [96]. The reaction was found to have a much broader scope
a
Pt(II)/Pt(IV)
manifold
(Scheme
48a)
[96].
The
reaction
was
found
to
have
a
much
broader
scope
than
the analogous palladium-catalyzed transformations, being tolerant of a wide range of both electron
than
the
analogous
palladium-catalyzed
transformations,
being tolerant
ofrange
a wide
range
of both
analogous
transformations,
being
tolerant
ofreversal
a wide
of both
electron
richtheand
electronpalladium-catalyzed
deficient arenes, and
furthermore,
a complete
in site-selectivity
was
electron
rich electron
and electron deficient
arenes,
furthermore,
a complete
reversal
site-selectivity
was
rich and
and and
furthermore,
a complete
reversal
in in
site-selectivity
was
observed
when usingdeficient
Na2PtClarenes,
4 versus Na2PdCl4 (Scheme 48b). The proposed mechanism proceeds
observed
when
using
NaNa
Na2 2PdCl
48b). The
Theproposed
proposedmechanism
mechanismproceeds
proceeds
2 PtCl
4 versus
44 (Scheme
when
using
2PtCl
4 versus Na
PdClC–C
(Scheme
viaobserved
a Pt(II)/Pt(IV)
redox
cycle
with
two-electron
bond 48b).
forming
reductive elimination,
analogous
via via
a Pt(II)/Pt(IV)
redox cycle
with two-electron
C–C
formingreductive
reductiveelimination,
elimination,analogous
analogous
a Pt(II)/Pt(IV)
cycle
two-electron
C–C bond
bond forming
to previous
work onredox
Pd(IV)
(seewith
Section
2.2.5) [72].
to previous
work
onon
Pd(IV)
(see
Section
to previous
work
Pd(IV)
(see
Section2.2.5)
2.2.5)[72].
[72].
a.
R
a.
R
Na 2PtCl 4 (2.5–5 mol %)
Na 2PtCl
(2.5–5 mol %)
[Ar 24I]TFA
[Ar 2I]TFA
Ar
R
Ar
R
AcOH or TFA
AcOH or TFA
Bu 4NOTf
42-85%
Bu 4NOTf
42-85%
Tolerant
of both
electron-rich
and
Tolerant
of both
electron-rich
and
electron-deficient
arenes
electron-deficient
arenes
b.
b.
Ph
[M]IV
Ph
[M]IV
[Ph
2I]TFA
[Ph 2I]TFA
+
Bu 4NOTf
Bu 4NOTf
[M]IV
[M]IV
Na 2PdCl
PdCl 4
Na
2
4
Na 2PtCl
PtCl 4
Na
2
4
Ph
105
Ph
+
106
105
106
25
25
1 1
11
1010
OptimizedNa
Na2PtCl
- 1:35with
with
65%
yield
2PtCl
Optimized
- 1:35
65%
yield
44
Scheme
48. (a)(a)
Intermolecular
C–H
arylation
with
Pt(II)
and diaryliodonium
diaryliodonium salts;(b)
(b) Reversal
of
site
Scheme
IntermolecularC–H
C–Harylation
arylationwith
withPt(II)
Pt(II) and
site
Scheme
48.48.
(a) Intermolecular
diaryliodoniumsalts;
salts; (b)Reversal
Reversalofof
site
selectivity
forfor
Pt(II)
vs.vs.
Pd(II)
selectivity
Pt(II)
Pd(II)ininarene
areneC–H
C–Hactivation.
activation.
selectivity for Pt(II) vs. Pd(II) in arene C–H activation.
Conclusion
3.3.3.3.
Conclusion
3.3. Conclusions
The
true
strength
thePt(II)/Pt(IV)
Pt(II)/Pt(IV)redox
redoxcouple
couple remains
remains in
forfor
more
The
true
strength
ofof
the
inits
itsuse
useas
asaamodel
modelcomplex
complex
more
The
true
strength
of
the
Pt(II)/Pt(IV)
redox
couple
remains
in
its
use
as
a
model
complex
for
reactive
Pd(II)/Pd(IV)
speciesdue
duetototheir
theirincreased
increased stability.
stability. However,
utility
reactive
Pd(II)/Pd(IV)
species
However,the
thepotential
potentialsynthetic
synthetic
utility
more
reactive
Pd(II)/Pd(IV)
species
due
to
their
increased
stability.
However,
the
potential
synthetic
of platinum
catalyzed
reactionsisisevident,
evident,having
havingdisplayed
displayed enhanced
selectivity
of platinum
catalyzed
reactions
enhancedreactivity,
reactivity,and
anddivergent
divergent
selectivity
utility
of platinum
catalyzed
reactions
isthat
evident,
having
displayed
enhanced λ
reactivity,
and divergent
3-iodanes produce
relative
to
palladium.
Dutton’s
findings
oxidation
employing
poly(cationic)
less
3
relative to palladium. Dutton’s findings that oxidation employing poly(cationic) λ -iodanes produce
less
selectivity
relative
to palladium.
Dutton’s
findings
thatmay
oxidation
employing
poly(cationic)
λ3 -iodanes
stable
Pt(IV)
centers
relative
to
traditional
oxidants
lead
to
more
reactive
Pt(IV)
intermediates
stable Pt(IV) centers relative to traditional oxidants may lead to more reactive Pt(IV) intermediates
produce
less stable
Pt(IV) centers
relative to
traditional oxidants may lead to more reactive Pt(IV)
and expand
their applications
in oxidative
couplings.
and expand their applications in oxidative couplings.
intermediates and expand their applications in oxidative couplings.
4. Gold
4. Gold
Gold
4.
4.1. Introduction
4.1. Introduction
Introduction
4.1.
Gold catalysis has historically proceeded through redox neutral pathways relying on its high
Gold catalysis
catalysis
has historically
historically
proceeded
through
redox neutral
neutral
pathways
relying
on its
itsand
high
Gold
has
through
redox
pathways
relying
on
high
efficiency
as a carbophilic
pi acid. proceeded
This has seen
wide application
in the
activation
of alkynes
efficiency
as
carbophilicattack
pi acid.
acid.
This
has seen
seen wide
wide cascades,
application
insynthetic
the activation
activation
of alkynes
alkynes
and
efficiency
carbophilic
pi
has
application
the
of
and
alkenes as
foraanucleophilic
andThis
cycloisomerization
andin
applications
of these
alkenes
for
nucleophilic
attack
and
cycloisomerization
cascades,
and
synthetic
applications
of
these
alkenes
for nucleophilic
attack and
cycloisomerization
cascades,
and synthetic
applications
of these
pathways
have been recently
reviewed
[97–100]. Reactions
containing
Au(I)/Au(III)
redox cycles
are
pathways
have
been recently
recently
reviewedof
[97–100].
Reactions
containing
Au(I)/Au(III)
redox
cycles
are
rare byhave
comparison,
a consequence
the high
barrier for
oxidation
of Au(I) to redox
Au(III)cycles
(redox
pathways
been
reviewed
[97–100].
Reactions
containing
Au(I)/Au(III)
are
rare
bycomparison,
comparison,
aTypical
consequence
of high
the
high
barrier
forelimination,
oxidation
oftoAu(I)
Au(III)
(redox
potential
+1.41 V).
oxidative
addition/reductive
areto(redox
ubiquitous
in
rare
by
a consequence
of the
barrier
for oxidation
of Au(I)which
Au(III)
potential
potential
+1.41chemistry,
V).
Typical
oxidative
addition/reductive
elimination,
which
ubiquitous
Pd(0)/Pd(II)
areaddition/reductive
thereby
challenging
with
Au(I)/Au(III)
(Scheme
49a, 107are
toin
109)
[101,102] in
+1.41
V). Typical
oxidative
elimination,
which
are ubiquitous
Pd(0)/Pd(II)
and examples
of suchare
reactivity
are
scarce [103–105].
Instead, Au(III)
complexes
via
Pd(0)/Pd(II)
chemistry,
thereby
challenging
with Au(I)/Au(III)
(Scheme
49a, can
107 be
to accessed
109) [101,102]
Au(I)
species,are
Lnscarce
–Au–X,[103–105].
to a powerful
external
and
contextvia
andexposure
examplesofofan
such
reactivity
Instead,
Au(III) oxidant,
complexes
caninbethis
accessed
hypervalent
iodine
reagents
haveLnfound
widespread
use, along
with hydroperoxides,
and
exposure
of an
Au(I)
species,
–Au–X,
to a powerful
external
oxidant, andSelectfluor,
in this context
hypervalent iodine reagents have found widespread use, along with hydroperoxides, Selectfluor, and
Molecules 2017, 22, 780
31 of 54
chemistry, are thereby challenging with Au(I)/Au(III) (Scheme 49a, 107 to 109) [101,102] and examples
of such reactivity are scarce [103–105]. Instead, Au(III) complexes can be accessed via exposure of
an Au(I) species, Ln –Au–X, to a powerful external oxidant, and in this context hypervalent iodine
Molecules
2017,
22, 780widespread use, along with hydroperoxides, Selectfluor, and others. A
31 of
54
reagents
have
found
catalytic
cycle based on this approach is shown in Scheme 49a; oxidation of Ln –Au–X gives Au(III) species 107,
others. A catalytic cycle based on this approach is shown in Scheme 49a; oxidation of Ln–Au–X gives
followed by two subsequent ligand exchanges to access 109, which would then undergo rapid reductive
Au(III) species 107, followed by two subsequent ligand exchanges to access 109, which would then
elimination
strategy
has led[102].
to developments
in led
alkynylation,
olefininfunctionalization,
undergo[102].
rapid This
reductive
elimination
This strategy has
to developments
alkynylation,
cross-couplings
and dimerization/homo-coupling
reactions using a wide reactions
range of using
oxidants
beyond
olefin functionalization,
cross-couplings and dimerization/homo-coupling
a wide
hypervalent
species
these reports
been
recently
reviewed
Gouverneur
[102].
range of iodine
oxidants
beyondand
hypervalent
iodinehave
species
and
these reports
have by
been
recently reviewed
Unfortunately,
advancements in reaction development centered on Au(I)/Au(III) have not
by Gouverneur [102].
Unfortunately,
advancements
in reaction
development
centered
on Au(I)/Au(III) have
not or
coincided with equivalent
mechanistic
understanding
of the
oxidation/reduction
pathways
coincided
with
equivalent
mechanistic
understanding
of
the
oxidation/reduction
pathways
speciation of the organometallic gold complexes involved. Oxidation potentials of activeorAu(I)
speciation
of theand
organometallic
gold
Oxidation
potentials
active Au(I)
species
species
are varied,
can depend
oncomplexes
both theinvolved.
counterion
and the
ligandofsphere,
making
proper
are varied, and can depend on both the counterion and the ligand sphere, making proper oxidant
oxidant selection delicate and the generation of isolable Au(III) species challenging and unpredictable.
selection delicate and the generation of isolable Au(III) species challenging and unpredictable.
However, pioneering studies by Hashmi [106,107], along with the synthesis and characterization of
However, pioneering studies by Hashmi [106,107], along with the synthesis and characterization of
stoichiometric
Au(III)
complexes
Lippert[109],
[109],Fuchita
Fuchita
[110],
Constable
stoichiometric
Au(III)
complexesbybyBennett
Bennett [108],
[108], Lippert
[110],
andand
Constable
[111],[111],
have have
laid the
foundations
for
a
more
in
depth
understanding
of
the
chemistry
of
these
highly
reactive
laid the foundations for a more in depth understanding of the chemistry of these highly reactive
intermediates
(Scheme
49b).
intermediates (Scheme 49b).
b. Stoichiometric Au(III) complexes
a. Au(I)/Au(III) catalytic cycle
R
R
L
Reductive
Elimination
AuI
Cl
X
[O]
R
Cl
109
X
R
AuIII
R
Direct
Oxidative
Addition
X
AuIII
107
L
R
X
AuIII
108
X
R
X
X
AuIII
N
N
S
O
NC
Me
O
Cl
Constable (1992)
X
Ligand
Exchange
AuIII
N
Cl
CN
N
Me
Lippert (1999)
R
X
Ligand
Exchange
Cl
X
L
X
S
N
N
L
AuIII
Me
Me PPh 2
AuI AuIII
Ph 2P
Me
Cl
AuIII
N
Cl
Me
[O] = hypervalent iodine, Selectfluor, peroxide
Bennett (2001)
Fuchita (2001)
Scheme 49. (a) Plausible Au(I)/Au(III) catalytic cycle based on use of an external oxidant; (b) Pioneering
Scheme 49. (a) Plausible Au(I)/Au(III) catalytic cycle based on use of an external oxidant;
examples of stoichiometric Au(III) complexes.
(b) Pioneering examples of stoichiometric Au(III) complexes.
4.2. Complex Synthesis and Characterization
4.2. Complex Synthesis and Characterization
Au(I) cationic salts, along with phosphine and N-heterocyclic carbene (NHC) supported Au(I)
complexes,
are the
most
utilized
Au(I)/Au(III)
catalysis.
NHC–Au(I)
chemistry
in particular
hasAu(I)
Au(I)
cationic
salts,
along
withinphosphine
and
N-heterocyclic
carbene
(NHC)
supported
gained immense
popularity
in the
last decade, making
them arguably
the most
well studied
of Au(I) has
complexes,
are the most
utilized
in Au(I)/Au(III)
catalysis.
NHC–Au(I)
chemistry
in particular
complexes.
strong σ–donation
the NHC
ligandthem
aides arguably
in stabilization
of both
Au(I) and
gained
immenseThe
popularity
in the lastofdecade,
making
the most
wellthe
studied
of Au(I)
Au(III)
species,
making
these
complexes
ideal
candidates
for
the
synthesis
of
isolable
complexes. The strong σ–donation of the NHC ligand aides in stabilization of both the Au(I) Au(III)
and Au(III)
complexes [112].
species, making these complexes ideal candidates for the synthesis of isolable Au(III) complexes [112].
Limbach and Nolan reported the synthesis of a range of NHC-Au(III) complexes via oxidation
Limbach and Nolan reported the synthesis of a range of NHC-Au(III) complexes via oxidation of
of an NHC–Au(I)–Cl with PhICl2 (Scheme 50, 110 → 113) [113,114]. The oxidation could also be
an NHC–Au(I)–Cl
PhICl
50, 110 →however
113) [113,114].
The oxidation
also be carried
2 (Scheme
at cryogenic
temperatures,
the oxidation
with PhIClcould
2 proceeded more
carried out withwith
Cl2(g)
out with
Cl2 (g)
at cryogenic
temperatures,
howevermaking
the oxidation
with
PhICl2 proceeded
more cleanly,
cleanly,
in higher
yield, and
at room temperature,
it far more
advantageous.
This advantage
in higher
yield, andtoatthe
room
temperature,
making itconditions
far more when
advantageous.
This
advantage
was attributed
relatively
milder oxidizing
using PhICl
2 versus
Cl2(g). was
Interestingly,
attemptedmilder
oxidations
with other
λ3-iodanes
suchusing
as Ph2PhICl
IBr, PhI(OAc)
2
,
and
PhI(OTFA)
2
attributed
to the relatively
oxidizing
conditions
when
versus
Cl
(g).
Interestingly,
2
2
3
either
failed
to
oxidize
the
Au(I)
complexes
or
gave
complex
product
mixtures.
The
authors
assert
attempted oxidations with other λ -iodanes such as Ph2 IBr, PhI(OAc)2 , and PhI(OTFA)2 either failed to
that
chlorine
ligands are or
crucial
stabilizeproduct
the Au(III)
center and
PhIClassert
2 is optimal as it acts as
oxidize
the
Au(I) complexes
gavetocomplex
mixtures.
Thethus
authors
that chlorine ligands
both
an
oxidant
and
chlorinating
agent.
NHC–Au(I)–Ph
complex
112
was
also
readily
oxidized
in and
are crucial to stabilize the Au(III) center and thus PhICl2 is optimal as it acts as
both an
oxidant
high yield with PhICl2 to give 113, which the authors state is the first reported Au(III) complex of the
chlorinating agent. NHC–Au(I)–Ph complex 112 was also readily oxidized in high yield with PhICl2 to
type [AuArCl2L] [113]. It is worth noting that trichloride Au(III) complex 111 could not be converted
Molecules 2017, 22, 780
32 of 54
give 113, which the authors state is the first reported Au(III) complex of the type [AuArCl2 L] [113]. It is
2017, 22, 780
32 of 54
worthMolecules
noting
that trichloride Au(III) complex 111 could not be converted to 113 via transmetalation
with Molecules
p-methoxyphenylmagnesium
bromide, instead giving rise to 4,40 -bismethoxybiphenyl32via
either
2017,transmetalation
22, 780
of 54
to 113 via
with p-methoxyphenylmagnesium bromide, instead giving rise to
4,4′a radical
coupling
or
inner-sphere
reductive
elimination
pathway.
bismethoxybiphenyl via either a radical coupling or inner-sphere reductive elimination pathway.
to 113 via transmetalation with p-methoxyphenylmagnesium bromide, instead giving rise to 4,4′Mesor inner-sphere reductive elimination OMe
Mes
bismethoxybiphenyl
via either a radical coupling
pathway.
N
AuI Cl
NMes
NR
AuI Cl
110
PhMgBr
N
96%
R
110
PhMgBr
Mes 96%
N
AuI Ph
NMes
NR
AuI Ph
112
N
R
PhICl 2
92-94%
PhICl 2
92-94%
PhICl 2
93%
PhICl 2
93%
N
Cl
N
AuIII
Mes
Cl
R ClN
N 111AuIII Cl
Cl
R Cl
111
N
(p-OMeC6H 4)MgBr
81%
(p-OMeC6H 4)MgBr MeO
81%
OMe
MeO
R = Mes,
Mes
Cl
N Mes
AuIII
Ph
R ClN
R = Mes,
N
N
113 III Cl
N
Au
Ph
R Cl
Scheme 50. Clean oxidation of NHC Au(I)
113complexes with PhICl2 by Nolan and Limbach.
Scheme
112 50. Clean oxidation of NHC Au(I) complexes with PhICl2 by Nolan and Limbach.
50.shown
Clean oxidation
of NHC
Au(I) complexes
with PhICl2 are
by Nolan
and Limbach.
It hasScheme
also been
by Nevado
that Au(III)
diacetate complexes
less stable
than the analogous
It
has also
been complexes
shown by(Scheme
Nevado51).
that
Au(III)
diacetate
complexes
are
less stable
than the
Au(III)
dichloride
Upon
oxidation
with PhICl
2, Au(III)
dichloride
complex
It
has
also
been
shown
by
Nevado
that
Au(III)
diacetate
complexes
are
less
stable
than
the
analogous
analogous
complexes
51). Upon
dichloride
115 is Au(III)
isolated dichloride
in high yields
(Scheme (Scheme
51a), however
use of oxidation
PhI(OAc)2 with
leadsPhICl
to isolation
of Au(III)
2 , Au(III)
Au(III)
complexes
51).
Upon
oxidation
withuse
PhICl
, (Scheme
Au(III) dichloride
complex
bispentafluorophenyl
119, via
Au(I)
mediated
transmetalation
51b)
[115].
Ligand
complex
115dichloride
is isolated
incomplex
high (Scheme
yields
(Scheme
51a),
however
of 2PhI(OAc)
leads
to
isolation
of
2
115
is isolated
in highto
yields
(Scheme
51a),
however
use
of PhI(OAc)
2 leads
to isolation
of Au(III)
exchange
is proposed
occur
through119,
twovia
possible
either
via
oxidation
of Au(I)
species
Au(III)
bispentafluorophenyl
complex
Au(I)pathways,
mediated
transmetalation
(Scheme
51b) [115].
bispentafluorophenyl
119,[Au(PPh
via Au(I)
transmetalation
51b)
[115]. Ligand
116exchange
to give 117isor
of acomplex
dissociated
3)2mediated
]+two
species
to
givepathways,
118. Both(Scheme
of
thesevia
complexes
would
Ligand
proposed
to occur
through
possible
either
oxidation
of Au(I)
exchange
is proposed
occur
through
two possible
pathways,
oxidation of Au(I)
species
then converge
to give to
119,
where
the chloride
atom (observed
ineither
X-rayvia
crystallography)
is proposed
+
species 116 to give 117 or of a dissociated [Au(PPh
)
]
species
to
give
118.
Both
of
these
complexes
3 2 to give 118. Both of these complexes would
116
to give
117solvent
or of aactivation.
dissociated [Au(PPh3)2]+ species
to come
from
would
then
converge
to
give
119,
where
the
chloride
atom (observed
in X-ray crystallography)
is
then converge to give 119, where the chloride atom (observed
in X-ray crystallography)
is proposed
a.
proposed
to
come
from
solvent
activation.
to come from solvent activation.
a. C6F 5
AuI PPh 3
Ph 3P
93%
PhICl 2
C6F 5
Ph 3P
93%
C6F 5
AuIII
Cl
Cl
115 Cl
AuIII
Cl
b.
114
115
Ph 3P
PhI(OAc) 2
Cl
AuIII
C6F 5 AuI PPh 3
C6F 5
39%
C6F 5
b.
119
116
Ph 3P
PhI(OAc) 2
Cl
AuIII
C6F 5 AuI PPh 3
C
F
39%
C
6 5
6F 5
Ph 3P
119
116 AuIII OAc
[AuIII(OAc) 4]
or
C6F 5
OAc
118
Ph 3P 117 OAc
III
after
III(OAc)
directAu
oxidation or oxidation
[Au
4]
dissociation
C6F 5
OAc
117
118
after
Scheme 51. (a) Oxidation of [Au(I)(C6F5direct
)PPhoxidation
3] with PhICloxidation
2; (b) Oxidation
of [Au(I)(C6F5)PPh3] with PhI(OAc)2.
dissociation
C6F 5
114
AuI PPh 3
PhICl 2
Scheme
51. (a)
Oxidation
of [Au(I)(C
6F52)PPh
3]become
with PhICl
(b) Oxidation
of [Au(I)(C
6F5generation
)PPh3] with PhI(OAc)
2.
Based
these
findings,
hasF
the2; reagent
of choice
for the
of isolable
Scheme
51.on(a)
Oxidation
of PhICl
[Au(I)(C
6 5 )PPh3 ] with PhICl2 ; (b) Oxidation of [Au(I)(C6 F5 )PPh3 ]
Au(III) complexes, particularly in the context of NHC complexes [112,116,117]. A noteworthy report
with PhI(OAc)2 .
on and
theseco-workers
findings, PhICl
2 has
become
for the investigation
generation of into
isolable
fromBased
Huynh
utilized
PhICl
2 as the
thereagent
oxidantofinchoice
a thorough
the
Au(III)
complexes,
particularly inproperties
the context
A noteworthy
report
structural
and electrochemical
ofofa NHC
rangecomplexes
of mono-[112,116,117].
and bis-NHC
Au(I) and Au(III)
Based
on these
findings,
become
the
reagent
of achoice
for
the
generation
of the
isolable
from
Huynh
and
co-workers
utilized
PhICl
2 as
theonoxidant
in
thorough
investigation
2 has
complexes.
This
report
is an PhICl
excellent
source
for
data
how oxidation
state,
NHC,
and halideinto
ligands
structural
and particularly
electrochemical
properties
a range
of
monoand
Au(I) discussion
and Au(III)
Au(III)
complexes,
in the
contextand
ofofNHC
complexes
[112,116,117].
noteworthy
report
effect
the properties
of NHC-Au
species,
the
reader
is directed
therebis-NHC
for a A
detailed
of from
complexes.
This
report
is
an
excellent
source
for
data
on
how
oxidation
state,
NHC,
and
halide
ligands
their
findings
[112].
Huynh and co-workers utilized PhICl2 as the oxidant in a thorough investigation into the structural and
effectDutton
the properties
of NHC-Au
species,
and the
reader
is directed
there
forasa detailed
discussion
and co-workers
recently
utilized
(poly)cationic
λ3-iodanes
neutral
ligand-donor
electrochemical
properties
of a range
of monoand
bis-NHC
Au(I)
and Au(III)
complexes.
Thisofreport
their
findings
[112].
oxidants
to
access
tricationic
Au(III)
complexes
[118].
The
same
group
has
used
these
oxidants
for
the
is an excellent source for data on how oxidation state, NHC, and3halide ligands effect the properties
of
andand
co-workers
recently (see
utilized
(poly)cationic
λ -iodanes
as neutral
ligand-donor
studyDutton
of Pd(IV)
Pt(IV) complexes
Section
3.1) and Ritter
also employed
these
reagents as
NHC-Au species, and the reader is directed there for a detailed discussion of their findings [112].
oxidants
Au(III)
complexes [118].C–H
The same
group has
these
oxidants
for the
oxidants to
in access
a high tricationic
profile study
on Pd(IV)-catalyzed
fluorination
(seeused
Section
2.2.3.1).
Oxidation
Dutton
and co-workers
recently utilized
(poly)cationic
λ3also
-iodanes
as neutral
ligand-donor
3
study
of
Pd(IV)
and
Pt(IV)
complexes
(see
Section
3.1)
and
Ritter
employed
these
reagents
as
of Au(I) complex 120 with three different (poly)cationic λ -iodanes possessing varied pyridine
oxidants
to
access
tricationic
Au(III)
complexes
[118].
The
same
group
has
used
these
oxidants
oxidants
in
a
high
profile
study
on
Pd(IV)-catalyzed
C–H
fluorination
(see
Section
2.2.3.1).
Oxidation
ligands resulted in complexes 121–123 (Scheme 52). This discovery is significant as prior attempts to
for the
study
of Pd(IV)
complexes
Section
3.1) and
Ritter also
of
Au(I)
complex
120 and
with
three
different
(poly)cationic
λ3-iodanes
possessing
varied
access
similar
complexes
viaPt(IV)
salt metathesis
on (see
halogenated
Au(III)
intermediates
ledemployed
to pyridine
complexthese
ligands
resulted inincomplexes
121–123
(Scheme
52). This discovery
is significant
as prior
to
reagents
as oxidants
a high profile
study
on Pd(IV)-catalyzed
C–H
fluorination
(seeattempts
Section 2.2.3.1).
access similar complexes via salt metathesis on halogenated Au(III) intermediates led to complex
Molecules 2017, 22, 780
33 of 54
Oxidation of Au(I) complex 120 with three different (poly)cationic λ3 -iodanes possessing varied
pyridine ligands resulted in complexes 121–123 (Scheme 52). This discovery is significant as prior
attempts to access similar complexes via salt metathesis on halogenated Au(III) intermediates led to
Molecules 2017, 22, 780
33 of 54
complex
decomposition, emphasizing the power of halide-free external oxidants in Au(I)/Au(III)
redox
chemistry
[117].
Cyclic
voltammetry
reveals
Au(III)/Au(I)
reduction
potentials
ranging
from
−
0.41
decomposition, emphasizing the power of halide-free external oxidants in Au(I)/Au(III) redox to
+ for 121–123 (reference 0.069 V vs. [Fc\Fc+ ] for [Au(III)/Au(I)][(dppe) ]), showing
−0.04chemistry
V vs. [Fc\Fc
[117].]Cyclic
voltammetry reveals Au(III)/Au(I) reduction potentials ranging from 2−0.41 to
+
a trend
that
mirrors
the
electron
donating
ability
ofVthe
pyridine
ligands ((121)NMe
−0.04 V vs. [Fc\Fc ] for 121–123
(reference
0.069
vs.different
[Fc\Fc+] for
[Au(III)/Au(I)][(dppe)
2]), showing
2 > (122)H >
a trend
that
mirrors the electron
donating
ability
the different
pyridine ligands
((121)NMe
2 > (122)H
(123)CN)
and
highlighting
the potential
to tune
theofreactivity
of tricationic
Au(III)
complexes
by varying
> (123)CN) and
highlighting
potential
to tune
the reactivity
of tricationic Au(III)
by
the heterocyclic
ligands.
Facile the
ligand
exchange
from
123 was demonstrated
withcomplexes
2,2,2-tripyridine
varying
the heterocyclic
ligands.subsequent
Facile ligand
exchangewith
fromH123
was
demonstrated
with
2,2,2- 125.
to give
124, which
could undergo
exchange
O
to
give
Au(III)–OH
complex
2
tripyridineoftoterminal
give 124,Au(III)–OH
which could complexes
undergo subsequent
exchange
with
H2O to give
Au(III)–OH
The synthesis
is rare and
previous
complexes
were
accessed via
complex 125. The synthesis of terminal Au(III)–OH complexes is rare and previous complexes were
salt metathesis with AgClO4 [119]. Intriguingly, homoleptic Au(III) complex (121) is stable to aqueous
accessed via salt metathesis with AgClO4 [119]. Intriguingly, homoleptic Au(III) complex (121) is
conditions, unlike Au(III) complexes (122 and 123). This distinction in reactivity also indicates that
stable to aqueous conditions, unlike Au(III) complexes (122 and 123). This distinction in reactivity
chemoselective
ligand
exchange could
be possible
these
also indicates
that chemoselective
ligand
exchangein
could
beAu(III)
possibletrications.
in these Au(III) trications.
NMe 2
R
OTf
2
2OTf
3
R
N
AuI
N
I
N
+
N
N
N
- PhI
N
AuIII
N
Me 2N
Potential vs Fc/Fc +
R
R
see table
R
NMe 2
120
R = CN
NMe 2
3
3
3OTf
OH
N
AuIII
H 2O
N
N
N
AuIII
N
N
125
124
3OTf
NMe 2
3OTf
N
E p,red (AuIII/I )
(121) –NMe2
(122) –H
(123) –CN
–0.41 V
–0.22 V
–0.04 V
125
0.21 V
N
N
N
Scheme 52. Dutton’s synthesis of tricationic Au(III) complexes and evaluation of their electrochemical properties.
Scheme
52.
Dutton’s synthesis of tricationic Au(III) complexes and evaluation of their
electrochemical properties.
4.3. Synthetic Applications
In 2008,
Beller and Tse developed the first gold catalyzed homo-coupling of arenes using HAuCl4
4.3. Synthetic
Applications
with PhI(OAc)2 as the external oxidant (Scheme 53a) [120,121]. Mechanistic insights hint that Au(III) is
In
Beller
and Tse developed
the that
firsta free
goldradical
catalyzed
of arenes
using
the2008,
active C–H
functionalization
catalyst and
cation homo-coupling
is not likely. PhI(OAc)
2 showed
the
highest
conversion
compared
to
other
oxidants
including
PhI(OTFA)
2
,
IBX
and
Oxone
and
HAuCl4 with PhI(OAc)2 as the external oxidant (Scheme 53a) [120,121]. Mechanistic insights hint
subsequent
studies
found
it was
essential that the external
be hypervalent
iodine
derived
[121].likely.
that Au(III)
is the
active
C–H
functionalization
catalystoxidant
and that
a free radical
cation
is not
More
recently,
Larrosa
and
co-workers
demonstrated
that
electron
deficient
arene-Au(I)
species
are, IBX
PhI(OAc)2 showed the highest conversion compared to other oxidants including PhI(OTFA)
2
capable of mediating hetero-coupling reactions with unactivated, electron-rich arenes utilizing
and Oxone
and subsequent studies found it was essential that the external oxidant be hypervalent
Koser’s reagent, PhI(OH)OTs, as the external oxidant (Scheme 53b) [122]. PhI(OPiv)2 also gave very
iodine derived [121]. More recently, Larrosa and
co-workers demonstrated that electron deficient
high yields in this transformation, however “F+” based oxidants Selectfluor and XeF2, as well as other
arene-Au(I)
species
are
capable
of
mediating
hetero-coupling
reactions with unactivated, electron-rich
acetate-ligated hypervalent iodine reagents (PhI(OAc)2, PhI(OTFA)2), were ineffective, again emphasizing
arenes
as the external
oxidantIt(Scheme
[122]. PhI(OPiv)
2
theutilizing
delicate Koser’s
nature ofreagent,
oxidant PhI(OH)OTs,
selection in high-valent
metal catalysis.
has also 53b)
demonstrated
that
+ ” based oxidants Selectfluor and
also gave
very
high
yields
in
this
transformation,
however
“F
silylated arenes are capable of undergoing arylation with a range of electron-deficient and electronXeF2 ,rich
as well
otherAu(I)/Au(III)
acetate-ligated
iodine
(PhI(OAc)
arenesasunder
redoxhypervalent
conditions, using
anreagents
in situ formed
oxidant
from PhI(OAc)
2 , PhI(OTFA)
2 ), 2were
and camphor
sulphonic acid the
(CSA)
(Scheme
53c) [123].
Other selection
carboxylate
of the PhI(O
2
ineffective,
again emphasizing
delicate
nature
of oxidant
inligands
high-valent
metal2CR)
catalysis.
also effective,that
however,
λ3-iodane
acidundergoing
and the “F+”arylation
oxidant Selectfluor
It hastype
alsowere
demonstrated
silylated
arenesiodosylbenzoic
are capable of
with a range
were completely ineffective,
producingarenes
none ofunder
the desired
product. redox conditions, using an in
of electron-deficient
and electron-rich
Au(I)/Au(III)
situ formed oxidant from PhI(OAc)2 and camphor sulphonic acid (CSA) (Scheme 53c) [123]. Other
carboxylate ligands of the PhI(O2 CR)2 type were also effective, however, λ3 -iodane iodosylbenzoic acid
and the “F+ ” oxidant Selectfluor were completely ineffective, producing none of the desired product.
Molecules 2017, 22, 780
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34 of 54
a. Beller, Tse (2008)
Me
2 mol% HAuCl 4
PhI(OAc) 2
Me
Me
81%
Me
Me
[O]
Me
b. Larrosa (2012)
F
OMe
3
NO 2
I
69%
1%
0%
OMe
F
AuIPHPh
Yield
PhI(OTFA) 2
IBX
Oxone
I
PhI(OH)OTs
85%
NO 2
c. Russell (2012)
TMS
R
R
1 mol%
PPh 3 AuOTs
PhI(OAc) 2, CSA
29-97%
R
R
Scheme 53.
53. (a)
(a) First
First example
example of
of aa gold
gold catalyzed
catalyzed homo-coupling
homo-coupling by
by Tse
Tse and
and Beller;
Beller; (b)
(b) Stoichiometric
Stoichiometric
Scheme
Au(I)-arene
hetero-coupling
of
unactivated
arenes
using
Koser’s
reagent;
(c)
Gold
catalyzed
arylation
Au(I)-arene hetero-coupling of unactivated arenes using Koser’s reagent; (c) Gold catalyzed arylation
of
silylated
arenes
with
electron-rich
and
electron-poor
arenes
by
Lloyd-Jones
and
Russell.
of silylated arenes with electron-rich and electron-poor arenes by Lloyd-Jones and Russell.
Nevado recently provided mechanistic insights into the role of various oxidants in Au(I)/Au(III)
Nevado recently provided mechanistic insights into the role of various oxidants in Au(I)/Au(III)
oxidative couplings (Scheme 54) [124]. Oxidation of Au(I) complex with PhI(OAc)2 in the presence of
oxidative couplings (Scheme 54) [124]. Oxidation of Au(I) complex with PhI(OAc)2 in the presence of
N-methylindole cleanly gave the hetero-coupling product (126) in 80% yield; this transformation was
N-methylindole cleanly gave the hetero-coupling product (126) in 80% yield; this transformation was
also successful using electron-rich arenes 1,3,5- and 1,2,5-trimethoxybenzene. Interestingly, the same
also successful using electron-rich arenes 1,3,5- and 1,2,5-trimethoxybenzene. Interestingly, the same
transformation using PhICl2 as the external oxidant was only applicable to N-methylindole as a
transformation using PhICl2 as the external oxidant was only applicable to N-methylindole as a
substrate. Upon oxidation to Au(III) 127, arene-auration can occur through two modes: (1) electrophilic
substrate. Upon oxidation to Au(III) 127, arene-auration can occur through two modes: (1) electrophilic
aromatic substitution to give 128 or (2) concerted C-H activation via 129, both of which converge to
aromatic substitution to give 128 or (2) concerted C-H activation via 129, both of which converge
give intermediate 130, which undergoes C–C bond-forming reductive elimination. The reactivity
to give intermediate 130, which undergoes C–C bond-forming reductive elimination. The reactivity
difference between PhI(OAc)2 and PhICl2 indicate that the basicity of the in-situ generated counterion
difference between PhI(OAc)2 and PhICl2 indicate that the basicity of the in-situ generated counterion
may play a key role and, analogous to Sanford’s work in Pd(II)/PhI(OAc)2 C–H activation [2], the
may play a key role and, analogous to Sanford’s work in Pd(II)/PhI(OAc)2 C–H activation [2],
acetate group may assist in the key activation step (129). This would account for the diminished
the acetate group may assist in the key activation step (129). This would account for the diminished
reactivity seen with PhICl2 in the case of substrates possessing less acidic C–H bonds such as 1,3,5reactivity seen with PhICl2 in the case of substrates possessing less acidic C–H bonds such as 1,3,5- and
and 1,2,5-trimethoxybenzene, and suggest that PhI(OAc)2 may be superior to PhICl2 for Au(III)1,2,5-trimethoxybenzene, and suggest that PhI(OAc)2 may be superior to PhICl2 for Au(III)-mediated
mediated C–H activation.
C–H activation.
Au(III)-catalyzed arene alkynylations have been reported by both Nevado [125] and Waser [126],
Au(III)-catalyzed arene alkynylations have been reported by both Nevado [125] and Waser [126],
employing PhI(OAc)2 and an alkynyl benziodoxolone respectively (Scheme 55). The development of
employing PhI(OAc)2 and an alkynyl benziodoxolone respectively (Scheme 55). The development
gold-mediated alkynylations of this type has been recently reviewed [127]. Nevado’s work used
of gold-mediated alkynylations of this type has been recently reviewed [127]. Nevado’s work used
PhI(OAc)2 as an oxidant to couple electron-withdrawn alkynes and unactivated, electron-rich arenes;
PhI(OAc)2 as an oxidant to couple electron-withdrawn alkynes and unactivated, electron-rich arenes;
oxidants including PhIO, Selectfluor, and TBHP gave significantly lower yields. Waser utilized a
oxidants including PhIO, Selectfluor, and TBHP gave significantly
lower yields. Waser utilized
slightly different approach wherein 1-[(triisopropylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one (TIPSa slightly different approach wherein 1-[(triisopropylsilyl)ethynyl]-1λ3 ,2-benziodoxol-3(1H)-one
EBX) served as both the oxidant and alkyne source, in the direct C3-alkynylation of indoles. Waser later
(TIPS-EBX) served as both the oxidant and alkyne source, in the direct C3-alkynylation of indoles.
extended this method to the alkynylation of other electron-rich heterocycles including thiophenes,
Waser later extended this method to the alkynylation of other electron-rich heterocycles including
anilines, and furans [128–130]. Although Au(I)/Au(III) redox couples are proposed in these cases via
thiophenes, anilines, and furans [128–130]. Although Au(I)/Au(III) redox couples are proposed in these
intermediates such as 132, Au(I) carbophilic pi activation cannot dismissed as subsequent α- or
cases via intermediates such as 132, Au(I) carbophilic pi activation cannot dismissed as subsequent αβ-elimination could provide the desired products via iodo-Au(I) intermediate 131.
or β-elimination could provide the desired products via iodo-Au(I) intermediate 131.
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N
N
Me
Me
C6F 5
C6F 5 PhI(OAc) 2
PhI(OAc) 2
AuI
AuI
PPh 3
PPh 3
N
NMe
Me
Ph 3P
Ph 3P AuIII
C6F 5 AuIII
C6F 5
127
127
N
126 NMe
126 Me
Ph 3P
OAc
Ph 3P AuIII OAc
C6F 5 AuIII
N Me
H
C6F 5
N Me
H
OAc
OAc
128
128
OAc
OAc
OAc
OAc
N
NMe
Me
C6F 5
C6F 5
Ph 3P AuI C6F 5
Ph 3P AuI C6F 5
PhI(OAc) 2
PhI(OAc) 2
80%
80%
Me
Me
Ph 3P
Ph
C63FP5
C6F 5
O
O
O
H
O
H
Au
Au
OAc N
OAc N
Me
Me
129
129
HOAc
HOAc
Ph 3P
OAc
Ph 3P AuIII OAc
III
C6F 5 Au
N Me
C6F 5
N Me
130
130
126
126
HOAc
HOAc
Scheme 54.
54. Proposed
Proposed mechanism
mechanism of
of Au(I)/Au(III)
Au(I)/Au(III) catalyzed
Scheme
catalyzed hetero-coupling
hetero-coupling of
of electron
electron rich
rich arenes.
arenes.
Scheme 54. Proposed mechanism of Au(I)/Au(III) catalyzed hetero-coupling of electron rich arenes.
Nevado (2010)
Nevado (2010)
OMe
OMe
MeO
MeO
OMe
OMe
5.0 mol%
[Au(PPh
5.0 mol%
3)Cl]
[Au(PPh
PhI(OAc)
3)Cl]
2
PhI(OAc) 2
R
R
OMe
OMe
MeO
MeO
R
R
OMe
OMe
Si(iPr) 3
Si(iPr) 3
Waser (2009)
Waser (2009)
AuIII
AuIII
5.0 mol% AuCl
5.0 mol% AuCl
N
H
N
H
(iPr) 3Si
(iPr) 3Si
I O
I O
Possible Intermediates
Possible Intermediates
AuI
[I]
AuI
[I]
R
R
131
131
via pi activation/elimination
via pi activation/elimination
O
O
N
H
N
H
Si(iPr) 3
Si(iPr) 3
132
132
via Au(I)/Au(III) redox cycle
via Au(I)/Au(III) redox cycle
Scheme 55. Oxidative alkynylation reactions by Nevado and Waser. Two potential pathways for
Scheme 55.
55. Oxidative
Oxidative alkynylation
alkynylation reactions
reactions by
by Nevado
Nevado and
and Waser. Two potential pathways for
Scheme
alkynylation
based upon Au(I) oxidation
or Au(I) pi
activation. Waser. Two potential pathways for
alkynylation based
based upon
upon Au(I)
Au(I) oxidation
oxidationor
orAu(I)
Au(I)pi
piactivation.
activation.
alkynylation
In 2009, Muñiz and Iglesias took advantage of highly reactive Au(III) complexes to develop a
In 2009, Muñiz and Iglesias took advantage of highly reactive Au(III) complexes to develop a
gold-catalyzed
alkeneand
diamination
reaction
(Schemeof
56),
analogous
to their
previous
report to
employing
In 2009, Muñiz
Iglesias took
advantage
highly
reactive
Au(III)
complexes
develop
gold-catalyzed alkene diamination reaction (Scheme 56), analogous to their previous report employing
(see alkene
Section diamination
2.2.4.1) [131].reaction
Alkenes (Scheme
underwent
intramolecular
withreport
tosylaPd(II)/Pd(IV)
gold-catalyzed
56),
analogous todiamination
their previous
Pd(II)/Pd(IV) (see Section 2.2.4.1) [131]. Alkenes underwent intramolecular diamination with tosylprotected
ureas
133
under
basic
conditions
using
[Au(OAc)PPh
3
]
to
give
bicyclic
ureas
(136)
in
high
employing Pd(II)/Pd(IV) (see Section 2.2.4.1) [131]. Alkenes underwent intramolecular diamination
protected ureas 133 under basic conditions using [Au(OAc)PPh3] to give bicyclic ureas (136) in high
yield.tosyl-protected
Redox neutralureas
anti-aminoauration
Au(I) using
intermediate
134, followed
irreversible
with
133 under basicgives
conditions
[Au(OAc)PPh
bicyclic
ureas
3 ] to giveby
yield. Redox neutral anti-aminoauration gives Au(I) intermediate 134, followed
by irreversible
oxidation
by PhI(OAc)
2 to Au(III)
135. Following
deprotonation,
SN2-type
intramolecular
(136)
in high
yield. Redox
neutraldiacetate
anti-aminoauration
gives
Au(I) intermediate
134,
followed by
oxidation by PhI(OAc)2 to Au(III) diacetate 135. Following deprotonation, SN2-type intramolecular
cyclization provides
cyclic
136diacetate
and regenerates
the Au(I)
catalyst. Although
the
irreversible
oxidationthe
by desired
PhI(OAc)
Au(III)
135. Following
deprotonation,
SN 2-type
2 to urea
cyclization provides the desired cyclic
urea 136 and regenerates the Au(I) catalyst. Although
the
proposed Au(III)
intermediates
werethe
toodesired
reactivecyclic
to beurea
isolated,
mechanistic
studies
using catalyst.
a PPh3–
intramolecular
cyclization
provides
136 and
regenerates
the Au(I)
proposed Au(III) intermediates were too reactive to be isolated, mechanistic studies using a PPh3–
Au(I)–Me the
complex
137 Au(III)
gave an
isomeric mixtures
ofreactive
Au(III) to
intermediates
138 and 139studies
upon
Although
proposed
intermediates
were too
be isolated, mechanistic
Au(I)–Me complex 137 gave an isomeric mixtures31 of Au(III) intermediates 138 and 139 upon
oxidation
with
PhI(OAc)complex
2, which 137
weregave
detectable
by P-NMR.
using
a PPh
an isomeric
mixtures of Au(III) intermediates 138 and 139
3 –Au(I)–Me
oxidation with
PhI(OAc)2, which were detectable by 31P-NMR.
upon oxidation with PhI(OAc)2 , which were detectable by 31 P-NMR.
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O
O
R
RR
R
H
N
H Ts
N
NH Ts
NH
136
136
Ts
Ts N
O N
O N
N
7.5 mol%
[Au(OAc)PPh
7.5 mol% 3]
PhI(OAc)
[Au(OAc)PPh
2, NaOAc
3]
PhI(OAc) 2, NaOAc
62-93%
133
62-93%
133
L AuIOAc
L AuIOAc
AcOH
AcOH
O
O
N
N
AuI L
AuI L
134
134
Ts
Ts NH
O NH
O N
N
AcOH
AcOH
OAc
OAc
136
136
133
133
Ts
HN
Ts
HN
L
OAc
LAuIII OAc
AuIIIOAc
OAc
R
RR
R
O
O
Ts
N
N
Ts
N
N
L
OAc
L AuIII OAc
AuIII OAc
OAc
PhI(OAc) 2
PhI(OAc) 2
Ph 3P
Ph 3P
Au(I) Me
Au(I) Me
137
137
PhI(OAc) 2
PhI(OAc) 2
Ph 3P
Me
III
Ph 3P Au Me 138
AcO AuIII OAc 138
AcO
OAc
Ph 3P
OAc
III
Ph 3P Au OAc 139
AcO AuIII Me
139
AcO
Me
Detected by 31P NMR
Detected by 31P NMR
135
135
Scheme 56.
56. Au(I)/Au(III)
Au(I)/Au(III) catalytic
Scheme
catalyticcycle
cycle for
for intramolecular
intramolecular diamination
diamination of
of olefins.
olefins.
Scheme 56. Au(I)/Au(III) catalytic cycle for intramolecular diamination of olefins.
An interesting example of C–C bond cleavage was demonstrated by Shi and co-workers with
An
example
of
by
with
An interesting
interesting
example
of C–C
C–C bond
bond cleavage
cleavage was
was demonstrated
demonstrated
by Shi
Shi and
and co-workers
co-workers
with
Au(I)/Au(III)
catalysis
and methylenecyclopropanes
(Scheme
57) [132]. Precomplexation
of alkene
to
Au(I)/Au(III)
(Scheme 57) [132]. Precomplexation
of
alkene
to
Au(I)/Au(III)
catalysis
and
methylenecyclopropanes
Precomplexation
of
alkene
to
Au(I) leads to a redox neutral allylic rearrangement to give 140, which is oxidized with PhI(OAc)2 to
Au(I)
leads
to
a
redox
neutral
allylic
rearrangement
to
give
140,
which
is
oxidized
with
PhI(OAc)
to
Au(I)Au(III)
leads to
a redox141.
neutral
allylic elimination
rearrangement
to141
givewould
140, which
is oxidized
with PhI(OAc)
22 to
give
diacetate
Reductive
from
give the
desired diacetate
142 with
give
Au(III)
diacetate
141.
Reductive elimination from 141 would give the desired
diacetate
142
with
give
Au(III)
diacetate
141.
desired
diacetate
142
with
regeneration of a [Au(I)(PMe3)OAc] catalyst.
regeneration
regeneration of
of aa [Au(I)(PMe
[Au(I)(PMe33)OAc] catalyst.
5.0 mol%
[Au(PMe
3)Cl]
5.0 mol%
PhI(OAc)
[Au(PMe
2
3)Cl]
PhI(OAc)
40-99% 2
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar 142
142
Ph
Ph
Ph
Ph
Ar
Ar
Ar
Ar 142
142
40-99%
OAc
OAc
OAc
OAc
L AuIOAc
L AuIOAc
AuClL
Ar
AuClL
Ar
Ar
Ar
HCl
HCl
Ph
Ph
Ph I
PhAu I
Au
OAc
L OAc
III
L Au OAc
AuIIIOAc
OAc
OAc
141
141
PhI(OAc) 2
PhI(OAc) 2
Ph
Ph
Ph
Ph 140
140
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
AuI L
AuI L
Scheme 57. Au(I)/Au(III) catalyzed diacetoxylation of methylenecyclopropanes via C–C bond cleavage.
Scheme
Au(I)/Au(III)
catalyzed
diacetoxylation
of methylenecyclopropanes
via C–C bondvia
cleavage.
Scheme57.57.
Au(I)/Au(III)
catalyzed
diacetoxylation
of methylenecyclopropanes
C–C
bond cleavage.
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4.4. Conclusions
4.4. Conclusions
Although advancements have been made toward mechanistic understanding of Au(I)/Au(III)mediated
oxidative
couplings, it ishave
clear that
of gold redoxunderstanding
chemistry are still
Although
advancements
beensynthetic
made applications
toward mechanistic
of
in
their
infancy.
As
methods
development
and
mechanistic
elucidation
in
this
field
the
Au(I)/Au(III)-mediated oxidative couplings, it is clear that synthetic applications continues,
of gold redox
choice
of external
oxidant
play a As
crucial
role as
it affects both
stability elucidation
of the reactive
Au(III)
chemistry
are still in
their infancy.
methods
development
and the
mechanistic
in this
field
intermediates
and
their
subsequent
reactivity
in
organic
transformations.
Thus
far,
PhICl
2 has emerged as
continues, the choice of external oxidant play a crucial role as it affects both the stability of the reactive
aAu(III)
leaderintermediates
for the isolation
Au(III)
complexes,
due the
reaction
conditions and
stabilization
andoftheir
subsequent
reactivity
in mild
organic
transformations.
Thus
far, PhICl2
imparted
by
the
transfer
of
chloride
ligands.
Conversely,
PhI(OAc)
2 is more efficient in catalytic
has emerged as a leader for the isolation of Au(III) complexes, due the mild reaction conditions and
manifolds
as imparted
the resultant
complexes
more reactive
andConversely,
acetate ligands
can assist
in key C–H
stabilization
by the
transfer are
of chloride
ligands.
PhI(OAc)
2 is more efficient
3
activation
The work
of resultant
Dutton incomplexes
the use of (poly)cationic
λ -iodanes
has laid
the groundwork
in catalyticsteps.
manifolds
as the
are more reactive
and acetate
ligands
can assist in
for
the
exploration
of
highly
tunable
Au(III)
complexes
and
this
discovery
could
lead
to new
3
key C–H activation steps. The work of Dutton in the use of (poly)cationic λ -iodanes has laid
the
developments
in
the
chemistry
of
cationic
Au(III)
intermediates.
groundwork for the exploration of highly tunable Au(III) complexes and this discovery could lead to
new developments in the chemistry of cationic Au(III) intermediates.
5. Nickel
5. Nickel
5.1. Introduction
5.1. Introduction
Nickel is a group 10 metal, the first-row counterpart of palladium. Low oxidation state nickel
is a group
10Ni(0)//Ni(I)/Ni(II),
metal, the first-rowhave
counterpart
of palladium.
Low oxidation
state nickel
redox
redoxNickel
couples,
such as
seen significant
applications
in catalysis,
including
couples,
such
as
Ni(0)//Ni(I)/Ni(II),
have
seen
significant
applications
in
catalysis,
including
Suzuki,
Suzuki, Negishi, and Kumada couplings, as well as recent advancements in radical mediated crossNegishi, and
Kumada
couplings,
well as recent
advancements processes
in radical has
mediated
cross-coupling
coupling
reactions
[133].
A recent as
resurgence
in nickel-catalyzed
been fueled
not only
reactions
[133].
A recent resurgence
in nickel-catalyzed
processes
hasunique
been fueled
not only
by its
by
its greater
sustainability
and economic
advantages, but
also by its
electronic
properties
greater
sustainability
economic to
advantages,
but counterpart.
also by its unique
properties
that
that
facilitate
reactivityand
inaccessible
its palladium
Unlikeelectronic
palladium,
which relies
facilitate
reactivity inaccessible
to itsredox
palladium
Unlike palladium,
relies almost
almost
exclusively
on two-electron
cycles,counterpart.
nickel can undergo
facile one-which
and two-electron
exclusively
onproviding
two-electron
redox
nickel Ni(II),
can undergo
oneand
two-electron
redox
events,
redox
events,
access
to cycles,
Ni(0), Ni(I),
Ni(III),facile
and in
rare
examples,
Ni(IV)
oxidation
providing
access58).
to Ni(0),
Ni(III),
and in rare
examples,
Ni(IV)ofoxidation
states
58).
states
(Scheme
WhileNi(I),
theseNi(II),
numerous
pathways
expand
the scope
reactivity,
they(Scheme
also make
While these numerous
pathways investigations
expand the scope
of reactivity,
they
alsorange
makeof
characterization
and
characterization
and mechanistic
difficult
due to the
wide
redox couples that
mechanistic
investigations
difficult due to
rangestate
of redox
couples
that could
invoked.
could
be invoked.
Recent advancements
in the
highwide
oxidation
palladium
chemistry
hasbesparked
a
Recent advancements
high
chemistry
has and
sparked
a renewed
renewed
investigationininto
theoxidation
synthesisstate
andpalladium
characterization
Ni(III)
Ni(IV)
species, investigation
which could
into theexpand
synthesis
characterization
Ni(III) and Ni(IV)
species,
which
could
expand the
the
greatly
theand
current
scope of nickel-catalyzed
reactions.
In this
section,
wegreatly
will highlight
current
of nickel-catalyzed
reactions.
thisserve
section,
weselection
will highlight
theeither
key role
both
key
role scope
that both
ligand scaffold and
oxidantIncan
in the
between
one-that
or twoligand scaffold
andas
oxidant
in the
between
or two-electron
pathways
as
electron
pathways
well ascan
theserve
stability
of selection
the resultant
higheither
valentonecomplexes.
Hypervalent
iodine
well as the
stability
of athe
resultant
highadvancement
valent complexes.
iodine
have played
oxidants
have
played
key
role in the
of thisHypervalent
field, analogous
to oxidants
their prominent
role
a key
in the advancement
of thiscatalysis
field, analogous
to their
role
the development
of
in
the role
development
of Pd(II)/Pd(IV)
(see Section
2.1).prominent
In order to
putinmodern
approaches
Pd(II)/Pd(IV)
catalysis
(see with
Section
2.1). history
In orderoftoisolated
put modern
approaches
context,
will begin
into
context, we
will begin
a brief
Ni(IV)
complexesinto
accessed
viawe
a variety
of
with a brief history of isolated Ni(IV) complexes accessed via a variety of methods.
methods.
Traditional Modes of Ni catalysis: Ni(0)/Ni(I)/Ni(II)
Ni
0
1 e–
Ni
I
1 e–
Ni
direct 2 e –
Ni
I
2
e–
II
Emerging area of research: Ni(II)/Ni(III)/Ni(IV)
Ni III
1 e–
Ni
II
2 e–
Ni IV
Common Oxidants:
HVI: PIDA, PhICl2
Non-HVI: TDTT, NFTPT, Br2
Ni
III
Scheme
Scheme 58.
58. Traditional
Traditional and
and emerging
emerging nickel
nickel oxidation
oxidation states
states invoked
invoked in
in catalysis,
catalysis, and
and common
common
oxidants
reported
in
the
literature.
oxidants reported in the literature.
Reports on the isolation of Ni(IV) complexes date back to the mid 1970’s, and these species were
Reports on the isolation of Ni(IV) complexes date back to the mid 1970’s, and these species
even proposed as intermediates in some of the first Ni(0) catalyzed cross coupling reactions. The first
were even proposed as intermediates in some of the first Ni(0) catalyzed cross coupling reactions.
diorganonickel (IV) complex was synthesized and isolated by Cordier in 1994 through oxidative
The first diorganonickel (IV) complex was synthesized and isolated by Cordier in 1994 through
addition of methyl iodide to a Ni(II) precursor with acylphenolato and trimethylphosphine ligands
oxidative addition of methyl iodide to a Ni(II) precursor with acylphenolato and trimethylphosphine
(Scheme 59) [134]. In this case, the rigid chelate ring contains a hard base and powerful σ-donating
ligands (Scheme 59) [134]. In this case, the rigid chelate ring contains a hard base and powerful
phosphine ligands that provide substantial stability to the high-oxidation nickel complex. In 1999,
Molecules 2017, 22, 780
38 of 54
σ-donating phosphine ligands that provide substantial stability to the high-oxidation nickel complex.
In 1999, Tanaka et al reported the first silylnickel(IV) complex (Scheme 59) through a proposed
Molecules
2017, 22, 780
of 54[135].
oxidative
addition
of 1,2-disilylbenzene to a Ni(dmpe)2 and subsequent elimination of38H
2
Again, this complex was stabilized by strong σ-donor ligands and a rigid chelate similar to
Tanaka et al reported the first silylnickel(IV) complex (Scheme 59) through a proposed oxidative
that of
Cordier,
and in both reports,
X-ray2 crystallographic
analysis of
confirmed
an octahedral
addition
of 1,2-disilylbenzene
to a Ni(dmpe)
and subsequent elimination
H2 [135]. Again,
this
geometry.
Inwas
2003,
Linden
an isolable
complex
three
sigma and
bonded
complex
stabilized
byreported
strong σ-donor
ligands Ni(IV)
and a rigid
chelatecontaining
similar to that
of Cordier,
norbonyl
ligands
in
a
pseudo-tetrahedral
geometry
(Scheme
59)
[136].
This
species
was
accessed
in both reports, X-ray crystallographic analysis confirmed an octahedral geometry. In 2003, Linden
◦ C. Along
via oxidation
of isolable
a tris(1-norbornyl)nickel(II)
complex
anionbonded
with Onorbonyl
with being
reported an
Ni(IV) complex containing
three sigma
in a pseudo2 at −60ligands
tetrahedral
59) [136].
species
was accessed
via oxidation
of ashielding
tris(1-norbornyl)
strong
σ-donorgeometry
ligands,(Scheme
the steric
bulkThis
of the
1-norbonyl
ligands
provides
necessary
nickel(II) complex
anion
with O2 at −60 °C. Along
withMost
being recently,
strong σ-donor
ligands, the steric
bulk isolated
of the
for stabilization
of the
trialkylnickel(IV)
species.
the Steigerwald
group
a
1-norbonyl
ligands
provides
shielding
necessary
for
stabilization
of
the
trialkylnickel(IV)
species.
Most
tetraalkyl aspirocyclononane Ni(IV) complex that is remarkably stable to oxygen and high temperatures
recently, the Steigerwald group isolated a tetraalkyl aspirocyclononane Ni(IV) complex that is
(Scheme 59) [137]. The complex was isolated as an intermediate in a Ni(0) catalyzed strain release
remarkably stable to oxygen and high temperatures (Scheme 59) [137]. The complex was isolated as an
ring-opening polymerization, formed via the combination of two molecules of substrate into a dimeric
intermediate in a Ni(0) catalyzed strain release ring-opening polymerization, formed via the
bismetallocyclopentane
nickel species.
The remarkable
stability
of this complex isnickel
attributed
to The
the high
combination of two molecules
of substrate
into a dimeric
bismetallocyclopentane
species.
degree
of
steric
shielding
afforded
by
the
large
alkyl
ligands.
From
these
reports,
common
features
remarkable stability of this complex is attributed to the high degree of steric shielding afforded by
emerge
stabilize
high
oxidation
state nickel
complexes:
strong which
σ-donor
ligands,
chelation,
thewhich
large alkyl
ligands.
From
these reports,
common
features emerge
stabilize
highrigid
oxidation
and steric
of the metal
Additionally,
these
examples
the unusual
state shielding
nickel complexes:
strongcenter.
σ-donor
ligands, rigid
chelation,
andhighlight
steric shielding
of the stability
metal of
center. Additionally,
these examples
highlight
the unusual
stability
the nickel–alkyl complexes.
bond, a feature
the nickel–alkyl
bond, a feature
not common
in late
transition
metaloforganometallic
Finally,
not
common
in
late
transition
metal
organometallic
complexes.
Finally,
a
wide
range
of
oxidants,
a wide range of oxidants, varied in mechanism and strength, were utilized to access these systems,
varied
in mechanism
and addition
strength, were
to access
these
systems, ranging
C–X
oxidative
ranging
from
C–X oxidative
to O2utilized
oxidation
at low
temperature.
Whilefrom
these
studies
provide
addition to O2 oxidation at low temperature. While these studies provide valuable evidence for the
valuable evidence for the viability of Ni(IV) species and the oxidants capable of accessing them, they
viability of Ni(IV) species and the oxidants capable of accessing them, they are not readily translatable
are not readily translatable to catalytic manifolds.
to catalytic manifolds.
O
Ni II
[O]
NiIV
[O] = MeI, RSi–H, O 2
PMe 3
Me
Ni IV
I
PMe 3
H 2Si
O
XX
Cordier (1994)
H 2Si
SiH2 Me
2
P
Ni IV
P
SiH Me 2
2
Tanaka (1999)
Ni IV
Br
R
Ni IV
R
Steingerwald (2009)
R=
Linden (2003)
Scheme
59. Examples
of isolated
organonickel
complexes.
Highly
rigid
ligand
scaffolds
and
Scheme
59. Examples
of isolated
organonickel
(IV)(IV)
complexes.
Highly
rigid
ligand
scaffolds
and
strong
strong
σ-donor
ligands
are
common
features
that
aid
in
stabilization
of
these
species.
σ-donor ligands are common features that aid in stabilization of these species.
Over the last 10 years, a renewed interest in this has focused on the subsequent reactivity and
Over
thesynthetic
last 10 years,
interest
in this
focused
on the
possible
utility aofrenewed
Ni(IV) species,
along
withhas
ligand
scaffolds
andsubsequent
oxidants thatreactivity
could be and
possible
synthetic
of Ni(IV)
species,
with
ligand scaffolds
and oxidants
that could
developed
into utility
viable catalytic
systems.
In along
this effort,
hypervalent
iodine reagents
have emerged
as be
developed
intocandidates
viable catalytic
In this effort,
hypervalent iodine reagents have emerged as
promising
for bothsystems.
species isolation
and catalysis.
promising candidates for both species isolation and catalysis.
5.2. Stoichiometric Studies
5.2. Stoichiometric
Studies
Continued
efforts in the stoichiometric synthesis and characterization of Ni(IV) complexes have
expanded toefforts
includein
their
reactivity,
particularly
in C–C and C–X bond
forming
reductive have
Continued
thesubsequent
stoichiometric
synthesis
and characterization
of Ni(IV)
complexes
eliminations. The most challenging element of this work has been species isolation and proof of either
expanded to include their subsequent reactivity, particularly in C–C and C–X bond forming reductive
Ni(II)/Ni(III) or Ni(II)/Ni(IV) redox couples, as these intermediates are highly reactive and short lived.
eliminations. The most challenging element of this work has been species isolation and proof of either
The Sanford group has spearheaded these efforts, building on their extensive work in high
Ni(II)/Ni(III)
Ni(II)/Ni(IV)
redox couples,
these
intermediates
are highly
short lived.
oxidationor
state
palladium chemistry.
Theyas
have
explored
the viability
of bothreactive
Ni(III) and
and Ni(IV)
Molecules 2017, 22, 780
39 of 54
The Sanford group has spearheaded these efforts, building on their extensive work in high
oxidation state palladium chemistry. They have explored the viability of both Ni(III) and Ni(IV)
manifolds as inexpensive analogues to Pd(IV) in C–X reductive eliminations. A 2010 report studied
Molecules 2017, 22, 780
39 of 54
the oxidation of complex 143 with an excess of PhICl2 , which yielded an approximately 2:1 mixture of
C–Clmanifolds
and C-Bras
reductive
elimination
60a) [138].
This represented
the first
example
inexpensive
analoguesproducts
to Pd(IV) (Scheme
in C–X reductive
eliminations.
A 2010 report
studied
of C–X
forming
reductive
elimination
nickel.
They
propose
the likely intermediacy
thebond
oxidation
of complex
143 with
an excessfrom
of PhICl
2, which
yielded
an approximately
2:1 mixture of a
of species
C–Cl and
C-Br
reductive
elimination
products oxidation
(Scheme 60a)
[138]. This
the first
Ni(III)
(144),
however
note
that two-electron
to Ni(IV)
(145)represented
cannot be ruled
out due
example
of
C–X
bond
forming
reductive
elimination
from
nickel.
They
propose
the
likely
to an inability to isolate the reactive intermediates. It is also noteworthy that both the chlorine ligands
intermediacy
of a Ni(III)and
species
(144), however
that in
two-electron
Ni(IV)
introduced
upon oxidation,
the bromine
ligandnote
present
complexesoxidation
144 and to
145,
were(145)
available
cannot be ruled out due to an inability to isolate the reactive intermediates. It is also noteworthy that
for C–X reductive elimination.
both the chlorine ligands introduced upon oxidation, and the bromine ligand present in complexes
A subsequent study by Sanford examined the oxidation of a Ni(PhPy)2 complex (146), which
144 and 145, were available for C–X reductive elimination.
can then undergo
competitive
C–X orexamined
C–C reductive
elimination
(Scheme
60b) [139]. The analogous
A subsequent
study by Sanford
the oxidation
of a Ni(PhPy)
2 complex (146), which can
palladium
complex
had
previously
been
shown
to
undergo
preferential
C–X
reductive
elimination
then undergo competitive C–X or C–C reductive elimination (Scheme 60b) [139].
The analogous
whenpalladium
exposed complex
to a variety
of oxidants,
including
iodine reagents
(see elimination
Section 2.2.3.1),
had previously
been
shown tohypervalent
undergo preferential
C–X reductive
and thus
studytoprovided
anoxidants,
excellent
comparison
of the iodine
reactivity
of these
two metals.
It was
whenthis
exposed
a variety of
including
hypervalent
reagents
(see Section
2.2.3.1),
and
thus
this
study
provided
an
excellent
comparison
of
the
reactivity
of
these
two
metals.
It
was
shown that upon oxidation with PhICl2 , complex 146 gave only trace C–Cl bond formation (3%, 147)
shown
that product
upon oxidation
withthat
PhICl
complex
146 gave
only trace C–Cl
bond formation
(3%, 147)of 146
and the
major
148 was
of2,C–C
reductive
elimination.
Interestingly,
oxidation
and
the
major
product
148
was
that
of
C–C
reductive
elimination.
Interestingly,
oxidation
of
with but
+
with other Cl sources, NCS or CuCl2 , provided no observable C–Cl products, showing146
a slight
other Cl+ sources, NCS or CuCl2, provided no observable C–Cl products, showing a slight but
significant divergence in reactivity of the hypervalent iodine oxidant. Again, in this study, no high
significant divergence in reactivity of the hypervalent iodine oxidant. Again, in this study, no high
oxidation state intermediates could be isolated or observed in situ, although the divergent reactivity
oxidation state intermediates could be isolated or observed in situ, although the divergent reactivity
fromfrom
that that
of palladium
may
suggest
of palladium
may
suggesta adifference
difference in
in mechanism.
mechanism.
a. Sanford (2009)
Cl
Path A: 1 e –
Ni (III)
N
4 equiv.
PhICl 2
Br
12 hr, 25 °C
Me
Ni II
N
143
Me
NiIII
N
144
N
53%
Br
N
Cl
Path B: 2 e –
Ni (IV)
N
+
Me
Cl
N
NiIV
Cl
Br
25%
N
Br
145
b. Sanford (2010)
via
Ni II
N
146
[O]
N
C 6H 6,
rt
Ni III
or Ni IV
+
N
N
N
No isolable
intermediates
[O]
147
Cl
yield C–X (147) (%)
148
yield C–C (148) (%)
PhICl 2
3
69
NCS
nda
68
nda
79
CuCl 2
and =
not detected
Scheme 60. C–X versus C–C bond forming reductive elimination from high oxidation state nickel.
Scheme 60. C–X versus C–C bond forming reductive elimination from high oxidation state nickel.
(a) Competitive C–Br vs. C–Cl bond formation; (b) Competitive C–Cl vs. C–C bond formation.
(a) Competitive C–Br vs. C–Cl bond formation; (b) Competitive C–Cl vs. C–C bond formation.
Recently, in a high-profile report, the same group succeeded in the isolation and characterization
of a Ni(IV)in
intermediate
uponreport,
oxidation
a diorganonickel(II)
complex
(Schemeand
61) [140].
At the
Recently,
a high-profile
theofsame
group succeeded
in the149
isolation
characterization
outset intermediate
of their study,upon
key insights
intoofthe
stability of 149 to complex
oxidation 149
were
obtained
cyclicAt the
of a Ni(IV)
oxidation
a diorganonickel(II)
(Scheme
61)via
[140].
+
voltammetry.
Observation
of
two
quasi-reversible
oxidation
peaks
at
−0.61
V
and
+0.27
vs.
Fc/Fc
outset of their study, key insights into the stability of 149 to oxidation were obtained via ,cyclic
representative of Ni(II)/Ni(III) and Ni(III)/Ni(IV) redox couples, is noteworthy as these potentials are
voltammetry.
Observation of two quasi-reversible oxidation peaks at −0.61 V and +0.27 vs. Fc/Fc+ ,
relatively low and hints that catalytic cycles with interchange between these redox states could be
representative of Ni(II)/Ni(III) and Ni(III)/Ni(IV) redox couples, is noteworthy as these
potentials
+
plausible. Initially, oxidation of 149 with hypervalent iodine reagents PhI(OAc)2, PhICl2, or F source
Molecules 2017, 22, 780
40 of 54
are
relatively
low
Molecules
2017, 22,
780and hints that catalytic cycles with interchange between these redox states could
40 ofbe
54
plausible. Initially, oxidation of 149 with hypervalent iodine reagents PhI(OAc)2 , PhICl2 , or F+ source
3
2 reductive elimination
NFTPT resulted in rapid
rapid C(sp
C(sp3)–C(sp2)) reductive
elimination to give cyclobutane 151, not allowing
allowing
for study of any
any intermediates.
intermediates. However, use of
of TDTT
TDTT resulted
resulted in
in formation
formation of
of aa stable
stable Ni(IV)–CF
Ni(IV)–CF33
1
19 F-NMR, before giving rise to the same cyclobutane
intermediate
intermediate 152
152 that
that was
was detectable
detectable by
by 1H- and 19F-NMR,
before
product 151. Further evidence for the intermediacy of a Ni(IV) species was provided through X-ray
crystallographic characterization of a complex possessing a tridentate tris(2-pyridyl) methane ligand,
ligand,
again upon oxidation
oxidation with TDTT
TDTT (not
(not shown).
shown). Although products of oxidation
oxidation with hypervalent
hypervalent
iodine reagents were not directly observed in this case, the analogous reactivity of complex 150 to
that of hypervalent iodine-mediated oxidation provides strong evidence that those reactions are also
proceeding
evidence
forfor
thethe
accessibility
of
proceedingvia
viaaaNi(II)/Ni(IV)
Ni(II)/Ni(IV) redox
redoxcouple.
couple.This
Thisstudy
studyprovides
providesclear
clear
evidence
accessibility
Ni(II)/Ni(IV)
catalysis
manifolds
andand
supports
further
efforts
for developing
reactions
that that
invoke
this
of Ni(II)/Ni(IV)
catalysis
manifolds
supports
further
efforts
for developing
reactions
invoke
pathway.
It also
that the
of novel
C–X bond-forming
reactions,
analogous
to those
this pathway.
It shows
also shows
thatdevelopment
the development
of novel
C–X bond-forming
reactions,
analogous
to
with
will likely
that are not
capable
of undergoing
competitive
thosePd(II)/Pd(IV),
with Pd(II)/Pd(IV),
willrequire
likely ligand
requirescaffolds
ligand scaffolds
that
are not
capable of undergoing
C–C
reductive
elimination.
competitive
C–C
reductive elimination.
Me
N
N
Ni II
Me
Me
[O]
N
N
149
E1 /2 = –0.61V, +0.27V vs Fc/Fc+
S
OTf –
TDTT CF3
Me
Ni IV
X1
C–C
reductive
elimination
X2
-[NiII ]
150
X = F/OTf, OAc, Cl
[O]
X1, X2
PhI(OAc) 2
OAc, OAc
PhICl 2
Cl, Cl
NFTPT
F, OTf
TDTT
OTf, CF 3
Me
Me
151
C(sp 3 ) – C(sp 2 )
bond formation
Me
rapid RE
no isolable
intermediates
N
N
Me
NiIV
OTf
CF 3
152
characterized in situ
Scheme 61.
61.Oxidation
Oxidationand
and
reductive
elimination
a Ni(IV)
intermediate
using hypervalent
Scheme
reductive
elimination
fromfrom
a Ni(IV)
intermediate
using hypervalent
iodine,
+
+
+
+
, and
CF
3 sources.
Rapid
and
selective
C–C
bond
formation
was
observed
in
the
case
of all
all
iodine,
F
, andFCF
sources.
Rapid
and
selective
C–C
bond
formation
was
observed
in
the
case
of
3
hypervalent iodine oxidants.
Sanford’s group has recently utilized tripyrazoylborate (Tp) as a supporting ligand to isolate Ni(IV)
Sanford’s group has recently utilized tripyrazoylborate (Tp) as a supporting ligand to isolate Ni(IV)
complex 153 and examine its competency in C(sp2)–CF3 reductive eliminations (Scheme 62a) [141].
complex 153 and examine its competency in C(sp2 )–CF3 reductive eliminations (Scheme 62a) [141].
Oxidation was examined with a variety of Ar–X species and it was found that only aryldiazonium
Oxidation was examined with a variety of Ar–X species and it was found that only aryldiazonium salts
salts and diaryliodonium salts were competent oxidants, with diaryliodonium salts giving superior
and diaryliodonium salts were competent oxidants, with diaryliodonium salts giving superior yields
yields of complex 154. This represents the first evidence of the accessibility of the Ni(II)/Ni(IV)
of complex 154. This represents the first evidence of the accessibility of the Ni(II)/Ni(IV) manifold
manifold under mild conditions with diaryliodonium salts. 154 was further shown to undergo clean
under mild conditions with diaryliodonium salts. 154 was further shown to undergo clean C–CF3 bond
C–CF3 bond formation upon heating and results suggest a two-electron reductive elimination
formation upon heating and results suggest a two-electron reductive elimination pathway. Sanford
pathway. Sanford also recently reported the oxidation of a TpNi(II)biphenyl complex 155 and its
also recently reported the oxidation of a TpNi(II)biphenyl complex 155 and its subsequent reactivity in
subsequent reactivity in C–O bond reductive elimination (Scheme 62b) [142]. Oxidation with
C–O bond reductive elimination (Scheme 62b) [142]. Oxidation with PhI(OTFA)2 for just 10 min at
PhI(OTFA)2 for just 10 min at 25 °C cleanly produced 156 in 50% isolated yield. In line with their
25 ◦ C cleanly produced 156 in 50% isolated yield. In line with their previous studies, intramolecular
previous studies, intramolecular C(sp2)–O coupling from 156 was slow, however 157 could be
C(sp2 )–O coupling from 156 was slow, however 157 could be detected upon heating, the result of C–O
detected upon heating, the result of C–O bond-forming reductive elimination followed by cyclization
bond-forming reductive elimination followed by cyclization and hemiketalization. It was also found
and hemiketalization. It was also found that the –OTFA ligand could under rapid displacement with
that the –OTFA ligand could under rapid displacement with a nucleophilic source of –CF3 , which
a nucleophilic source of –CF3, which would then undergo slow C–CF3 reductive elimination (not
would then undergo slow C–CF3 reductive elimination (not shown). Taken together, these two reports
shown). Taken together, these two reports show the relatively facile access of the Ni(II)/Ni(IV)
show the relatively facile access of the Ni(II)/Ni(IV) manifold with hypervalent iodine reagents and
manifold with hypervalent iodine reagents and lend strong support for the development of diverse
lend strong support for the development of diverse catalytic reactions via this pathway. Furthermore,
catalytic reactions via this pathway. Furthermore, the tripyrazoylborate ligand is emerging as an
the tripyrazoylborate ligand is emerging as an excellent choice for stabilization and isolation of high
excellent choice for stabilization and isolation of high oxidation state nickel complexes.
oxidation state nickel complexes.
Molecules 2017, 22, 780
41 of 54
Molecules 2017, 22, 780
Molecules 2017, 22, 780
41 of 54
41 of 54
a. Sanford (2015)
a. Sanford (2015)
N
H
N
H B
B N
NN
N
N N
N N
I
I
NBu 4
NBu 4
N
N
BF 4
BF 4
N
H
NN
H B
N
B N
CF3
N
N
N NiIV CF3
N N
NiIV CF3
N N
CF3
CF3
55 °C
Ni II CF3
55 °C
–35 °C, 10 min
Ni II CF3
–Ni(II)
–35 °C,
10
min
–Ni(II)
CF3
77%
153
77%
154
153
154
1
13
Use of other Ar–X oxidants
characterized by H, C, 11 B, 19 F NMR
1 H, 13C, 11 B, 19 F NMR
Use of other Ar–X oxidants
characterized
by
and x-ray crystallography
X
N 2 BF 4
and x-ray crystallography
X
N 2 BF 4
X= Br, I, OTf
X= Br,
<1%I, OTf
42%
<1%
42%
b. Sanford (2017)
b. Sanford (2017)
N
H
N
H B
B N
NN
N
N N
N N
F 3C
F 3C
K
K
N
N
Ni II
Ni II
O
O
CF3
O I O
CF3
I
O
O
O
O
N
H
N
H B
B N
NN
N
N N
N N
10 min, 25 °C
10 min, 25 °C
50 %
50 %
155
155
CF3
CF3
O
O
N
N
Ni IV
Ni IV
O
O
CF3
CF3
CF3
3
O CFOH
OH
O
70 °C, 6 h
70 °C, 6 h
–Ni(II)
–Ni(II)
156
156
157
157
Scheme
Use
of tripyrazoylborate
(Tp)
ligand
in synthesis
the synthesis
characterization
of Ni(IV)
Scheme
62.62.
Use
of tripyrazoylborate
(Tp)
ligand
in the
and and
characterization
of Ni(IV)
species
Scheme
62.
Use
of tripyrazoylborate
(Tp)
ligand
in the synthesis
and characterization
of Ni(IV)
species
via
oxidation
with
hypervalent
iodine
reagents.
(a)
Use
of
diaryliodonium
salts;
(b)
Use of .
viaspecies
oxidation
with
hypervalent
iodine
reagents.
(a)
Use
of
diaryliodonium
salts;
(b)
Use
of
PhI(OTFA)
via oxidation with hypervalent iodine reagents. (a) Use of diaryliodonium salts; (b) Use of 2
PhI(OTFA)2.
PhI(OTFA)2.
Taking
ability of
of N-heterocyclic
N-heterocycliccarbenes
carbenes(NHCs),
(NHCs),
Alison
Takingadvantage
advantageofofthe
theexcellent
excellent σ-donor
σ-donor ability
Alison
Takingreported
advantage
of
the excellent
σ-donor
ability
of N-heterocyclic
carbenes
(NHCs), Alison
Fout’s
group
the
isolation
of
Ni(IV)
complex
159
and
its
reactivity
has
an
electrophilic
halogen
Fout’s group reported the isolation of Ni(IV) complex 159 and its reactivity has an electrophilic
Fout’s group
reported
the isolation
of Ni(IV) complex
and its reactivity
an electrophilic
surrogate
(Scheme
63) [143].
characterization
of159
Ni(II)
viahas
cyclic
voltammetry
halogen surrogate
(Scheme
63) Initial
[143]. Initial
characterization
of Ni(II)species
species158
158 via
cyclic
voltammetry
halogen surrogate (Scheme 63) [143]. Initial characterization of Ni(II) species
via cyclic voltammetry
+158
+, which
revealed
oxidationwave
waveatat+0.57
+0.57
Fc/Fc
, which
was attributed
revealedonly
onlyaasingle
single reversible
reversible oxidation
VV
vs.vs.
Fc/Fc
was
attributed
to the to
revealed only a single reversible oxidation wave at +0.57 V vs. Fc/Fc+, which was attributed to the
theNi(II)/Ni(III)
Ni(II)/Ni(III)
couple.
Thus,
it was somewhat
thatoftreatment
of 158 outer-sphere
with common
couple.
Thus, it
was somewhat
surprisingsurprising
that treatment
158 with common
Ni(II)/Ni(III) couple. Thus, it was somewhat
surprising+that treatment
of 158 with common outer-sphere
+, or Fc
one-electronone-electron
oxidants such
as Ag+,such
Ph3Cas
, was
treatment
of 158
with
outer-sphere
oxidants
Ag+ ,+Ph
, or Fc+ , was However,
unsuccessful.
However,
treatment
3 C unsuccessful.
one-electron oxidants such as Ag+, Ph3C+, or Fc+, was
unsuccessful. However, treatment of 158 with
2 resulted
clean two-electron
oxidation oxidation
to give 159,
which
was
characterized
by X-ray by
of PhICl
158 with
PhICl2inresulted
in clean two-electron
to give
159,
which
was characterized
PhICl2 resulted in clean two-electron oxidation to give 159, which was characterized by X-ray
crystallography.
This result
was the
first
evidence
that hypervalent
iodine reagents
were
X-ray
crystallography.
This result
was
thedefinitive
first definitive
evidence
that hypervalent
iodine reagents
crystallography. This result was the first definitive evidence that hypervalent iodine reagents were
competent
oxidants
in
the
Ni(II)/Ni(IV)
redox
couple.
Also
notable
is
the
significantly
higher
were
competent
oxidants
in the
Ni(II)/Ni(IV)
redox
couple.
Also
notable
is the
significantly
higher
competent
oxidants
in the
Ni(II)/Ni(IV)
redox
couple.
Also
notable
is the
significantly
higher
oxidation
potentialofof158
158relative
relativeto
tothat
that of
of 149
149 (see
Scheme
61)
and
yet
PhICl
2 was still a competent
oxidation
potential
(see
Scheme
61)
and
yet
PhICl
was
still
a
competent
oxidation potential of 158 relative to that of 149 (see Scheme 61) and yet PhICl2 2was still a competent
oxidant.InInthe
thecontinued
continueddevelopment
development of this
field, ititwill
toto
continue
to to
obtain
oxidant.
willlikely
likelybe
beimportant
important
continue
obtain
oxidant. In the
continued development of
of this
this field,
field, it will
likely
be
important
to continue
to obtain
electrochemical
measurements
of
both
hypervalent
iodine
reagents
and
metal
complexes,
which
electrochemical
measurements
of of
both
hypervalent
iodine
reagents
andand
metal
complexes,
which
could
electrochemical
measurements
both
hypervalent
iodine
reagents
metal
complexes,
which
could then be used as a predictive tool for the success of the subsequent oxidation.
then
be
used
as
a
predictive
tool
for
the
success
of
the
subsequent
oxidation.
could then be used as a predictive tool for the success of the subsequent oxidation.
iPr
iPr
N
N
N
N
N
N
NiII
NiII
Cl
iPr Cl iPr
iPr
iPr
N
N
iPr
iPr
PhICl 2
PhICl 2
158
158
Ni(II) / Ni(III) --> E1 /2 = +0.57 V vs Fc/Fc +
Ni(II) / Ni(III) --> E1 /2 = +0.57 V vs Fc/Fc +
iPr
iPr
N
N
NCl
N
IV
N
N Cl Ni
IV
Cl
Ni
N
Cl Cl N
iPr Cl iPr
iPr
iPr
iPr
iPr
159
159
Scheme 63. Two electron oxidation of Ni(II) monoanionic bis(carbene) pincer complex with PhICl2
Scheme 63. Two electron oxidation of Ni(II) monoanionic bis(carbene) pincer complex with PhICl2
Scheme
63. Two electron
oxidation
Ni(II) monoanionic
bis(carbene) pincer complex with PhICl2
and characterization
of stable
Ni(IV)ofintermediate
159.
and characterization of stable Ni(IV) intermediate 159.
and characterization of stable Ni(IV) intermediate 159.
5.3. Synthetic Applications
5.3. Synthetic Applications
5.3. Synthetic
Applications
Catalytic
cycles, and thus also synthetic applications, invoking high oxidation state nickel
Catalytic cycles, and thus also synthetic applications, invoking high oxidation state nickel
intermediates
remain
quitethus
rare. However,
building
on the body
of work high
in stoichiometric
complex
Catalytic cycles,
synthetic
applications,
invoking
oxidation state
nickel
intermediates
remainand
quite rare.also
However,
building
on the body
of work in stoichiometric
complex
synthesis,
such
reports
are
beginning
to
emerge,
but
the
oxidation
states
in
play
are
difficult
to
intermediates
remain
quite
rare.
However,
building
on
the
body
of
work
in
stoichiometric
complex
synthesis, such reports are beginning to emerge, but the oxidation states in play are difficult to
Molecules 2017, 22, 780
42 of 54
Molecules 2017,
22, 780
42 of 54 to
synthesis,
such
reports are beginning to emerge, but the oxidation states in play are difficult
Molecules
2017, 22,
780outline recent catalytic reports invoking both Ni(III) and Ni(IV) intermediates
42 of 54
discern.
Below
we
via
discern. Below we outline recent catalytic reports invoking both Ni(III) and Ni(IV) intermediates via
oxidation with hypervalent iodine reagents as well as synthetically relevant applications involving
oxidation
with hypervalent
iodinecatalytic
reagentsreports
as well
as synthetically
relevant
applications
involving
discern. Below
we outline recent
invoking
both Ni(III)
and Ni(IV)
intermediates
via
stoichiometric
complexes.
stoichiometric
oxidation withcomplexes.
hypervalent iodine reagents as well as synthetically relevant applications involving
The Nocera group reported the catalytic photoelimination of Cl2 from a Ni(III) intermediate,
The Nocera
group reported the catalytic photoelimination of Cl2 from a Ni(III) intermediate,
stoichiometric
complexes.
accessed via one-electron oxidation of a Ni(II) species with PhICl2 (Scheme 64) [144]. In this case,
accessed
via
one-electron
oxidation
a Ni(II) photoelimination
species with PhIClof2 (Scheme
[144]. intermediate,
In this case,
The Nocera group reported
theofcatalytic
Cl2 from 64)
a Ni(III)
careful
control
of
the
equivalents
ofPhICl
PhICl
for
selective
transfer
of a single
chlorineItatom.
2 allows
careful
control
of
the
equivalents
of
2
allows
for
selective
transfer
of
a
single
chlorine
is
accessed via one-electron oxidation of a Ni(II) species with PhICl2 (Scheme 64) [144]. Inatom.
this case,
It is
also
possible
that
the
ligand
scaffold
does
not
lower
the
oxidation
potential
far
enough
to
make
also
possible
that
ligand scaffold
does2 not
lower
oxidation
potential
far enough
makeIt ais a
careful
control
of the equivalents
of PhICl
allows
for the
selective
transfer
of a single
chlorinetoatom.
subsequent
Ni(III)/Ni(IV)
oxidation
accessible
in
this
case,
however
electrochemical
measurements
subsequent
Ni(III)/Ni(IV)
oxidation
accessible
this case,
however potential
electrochemical
measurements
also possible
that the ligand
scaffold
does notinlower
the oxidation
far enough
to make aon
this
complex
were
not
provided.
on
this complex
were not provided.
subsequent
Ni(III)/Ni(IV)
oxidation accessible in this case, however electrochemical measurements
on this complex were not provided.
0.5 PhICl 2
0.5 PhI
0.5 PhI
0.5 PhICl 2
Cl
P
Cl P
Cl
P
Ni II
P
Cl
Ni II
ΔH = + 23.7kcal.mol-1
ΔH = + 23.7kcal.mol-1
Cl
P
ClP
NiIII
P
Cl P
Cl
NiIII
Cl
Cl
hν
0.5 Cl 2
hν
0.5 Cl 2
Cl
Cl
P
Cl
P
P
ClP
NiIII
P
Cl
NiIII
Cl
Cl
Ni III
P
Cl
Ni III
Cl
Cl
Cl P
Cl P
Scheme
Photoeliminationof
ofCl
Cl2 via
via single
single electron
cycle
mediated
by by
PhICl
2.
Scheme
64.64.
Photoelimination
electronNi(II)/Ni(III)
Ni(II)/Ni(III)
cycle
mediated
PhICl
2
2.
Scheme 64. Photoelimination of Cl2 via single electron Ni(II)/Ni(III) cycle mediated by PhICl2.
Chatani’s group invoked a Ni(II)/Ni(IV) catalytic cycle in their development of a directed C(sp3)–
Chatani’s
group
invoked a Ni(II)/Ni(IV)
catalytic
cycle in their
developmentsalts
of a directed
H arylation
with
diaryliodonium
salts (Scheme
65)
[145].
of diaryliodonium
Chatani’s
group
invoked a Ni(II)/Ni(IV)
catalytic
cycleAinvariety
their development
of a directedbearing
C(sp3)–
3 )–H
C(sp
arylation
with
diaryliodonium
salts
(Scheme
65)
[145].
A
variety
of
diaryliodonium
salts
different
counter
ions
such were examined,
however
high
yields
only
in the case
of triflate,
H arylation
with
diaryliodonium
salts (Scheme
65)
[145].
A were
variety
of obtained
diaryliodonium
salts
bearing
bearing
different
counter
ions
such
were
examined,
however
high
yields
were
only
obtained
in
presumably
due toions
thesuch
necessary
regeneration
of the Ni(OTf)
2 catalyst.
Although
no in
intermediates
werethe
different counter
were examined,
however
high yields
were only
obtained
the case of triflate,
case
of triflate,
presumably
due with
to
the
necessary
regeneration
of theproviding
Ni(OTf)
catalyst.
Although
isolated,
radical
trap
experiments
TEMPO
gave
TEMPO-adducts,
least preliminary
presumably
due
to the
necessary
regeneration
of theno
Ni(OTf)
2 catalyst. Although
no2at
intermediates
were
noevidence
intermediates
were
isolated,
radical
trap
experiments
with
TEMPO
gave
no
TEMPO-adducts,
againsttrap
one-electron
pathways.
isolated, radical
experiments
with TEMPO gave no TEMPO-adducts, providing at least preliminary
providing
least preliminary
against one-electron pathways.
evidenceatagainst
one-electronevidence
pathways.
R
Ni(OTf) 2, Na 2CO3
O
ON
R
H
R
H N
H
H
MesCONa
2H CO
Ni(OTf)
2,
2
3
R
N
N
2H
ArMesCO
I
OTf
Ar Ph
I
OTf
21-72% yield
Ph
21-72% yield
R
O
ON
R
H
R
Ar N
H
Ar
R
N
N
Ph
Ph
Ph
Ph
O
ON
N
Ni
N
Ar
Ni OTfN
Possible Ni(IV)
Arintermediate
OTf
Possible Ni(IV) intermediate
Scheme 65. C(sp3)–H arylation with diaryliodonium salts through a proposed Ni(II)/Ni(IV) catalytic cycle.
3)–H arylation with diaryliodonium salts through a proposed Ni(II)/Ni(IV) catalytic cycle.
Scheme 65.
3 )–H arylation with diaryliodonium salts through a proposed Ni(II)/Ni(IV)
Scheme
65.C(sp
C(sp
Continuing their work in oxidative fluorination chemistry (for palladium analogue see Section
catalytic cycle.
2.2.3.1),
the Ritter group
reported
the development
of achemistry
one-step oxidative
radiofluorination
of arenes
Continuing
their work
in oxidative
fluorination
(for palladium
analogue see
Section
18F, and poly(cationic) N-ligated λ3-iodane 161 as the
employing
160 with
2.2.3.1), theNi(II)
Rittercomplex
group reported
theaqueous
development
of a one-step oxidative radiofluorination of arenes
Continuing
their
work
inone-step
oxidative
fluorination
chemistry
(for palladium
analogue
18F, and bond
3-iodane
oxidant
(Scheme
66)
[146].
This
oxidation/C–F
formationN-ligated
proceeds
via
the two-electron
employing
Ni(II)
complex
160
with
aqueous
poly(cationic)
λ
161 as thesee
Section
2.2.3.1),
the66)
Ritter
group
reportedoxidation/C–F
theiodine
development
of
a one-step
oxidative
radiofluorination
oxidation
of 160
by[146].
cationic
161,bond
which
undergoes
ligand
exchange
with
oxidant
(Scheme
This hypervalent
one-step
formation
proceeds
via the
two-electron
18 F, and poly(cationic) N-ligated
3 -iodane
3-iodane
ofnucleophilic
arenes
employing
Ni(II)
complex
160
with
aqueous
λ
fluoride
and
subsequent
reductive
elimination.
The
use
of
(poly)cationic
λ
161
oxidation of 160 by cationic hypervalent iodine 161, which undergoes ligand exchange with
18
3
161
as
the
oxidant
(Scheme
66)
[146].
This
one-step
oxidation/C–F
bond
formation
proceeds
via
elimination could
easily
be outcompeted
by the –X
isnucleophilic
critical in this
case asand
thesubsequent
desired F reductive elimination.
fluoride
The use
of (poly)cationic
λ -iodane
161the
18F
two-electron
of the
160
bycenter
cationic
hypervalent
iodine could
161, which
undergoes
ligand
ligands
transferred
to the
metal
with
traditional
hypervalent
iodine
(i.e.,
–Cl,
–OAc,
reductive
elimination
easilycomplexes
be outcompeted
byexchange
the –X
is critical
inoxidation
this case
as
desired
–OTFA)
[40]. Instead
transfers
two “innocent”
heterocyclic
ligands, allowing
the
ligands transferred
to complex
the metal161
center
with traditional
hypervalent
iodine complexes
(i.e., –Cl,for
–OAc,
–OTFA) [40]. Instead complex 161 transfers two “innocent” heterocyclic ligands, allowing for the
Molecules 2017, 22, 780
43 of 54
with nucleophilic fluoride and subsequent reductive elimination. The use of (poly)cationic λ3 -iodane
161 is critical in this case as the desired 18 F reductive elimination could easily be outcompeted by
the –X ligands transferred to the metal center with traditional hypervalent iodine complexes (i.e., –Cl,
Molecules 2017, 22, 780
43 of 54
–OAc, –OTFA) [40]. Instead complex 161 transfers two “innocent” heterocyclic ligands, allowing for the
challenging
challengingC–F
C–F reductive
reductiveelimination
eliminationto
toproceed
proceedin
inhigh
high yield.
yield. Even
Even though
though the
the detailed
detailed mechanistic
mechanistic
studies
studies were
were not
not reported,
reported, the
the formation
formation of
of Ni(IV)
Ni(IV) intermediate
intermediate 162
162 is
is reasonable
reasonable by
by analogy
analogy to
to their
their
3 -iodanes as two-electron oxidants
prior
reports,
as
well
as
work
by
Dutton
employing
(poly)cationic
λ
prior reports, as well as work by Dutton employing (poly)cationic λ3-iodanes as two-electron
in
the generation
of Pd(IV)ofand
Pt(IV)
species
Section
3.1). This
work
promise
of the
oxidants
in the generation
Pd(IV)
and
Pt(IV)(see
species
(see Section
3.1).
Thisshows
work the
shows
the promise
3 -iodanes as powerful oxidants that allow for challenging
relatively
unexplored
class
of
(poly)cationic
λ
3
of the relatively unexplored class of (poly)cationic λ -iodanes as powerful oxidants that allow for
reductive
eliminations
that would be
precluded
with
the use with
of more
oxidants.
challenging
reductive eliminations
that
would be
precluded
thecommon
use of more
common oxidants.
O
N
S
O
S
NO 2
N Ni II N
1.5 equiv N-HVI (161)
aqueous 18F –, 18-cr-6
MeCN
23 oC, <1min
160
Ph
2 OTf –
O
Ph
N
N
N
F
65%
OMe
MeO
N Py
2
2 OTf
O
NO 2
OMe
Ni IV
N
Py
162
Ar
Py =
N
Possible Ni(IV) intermediate analogous
to Pd(IV)-mediated transformation
I
N-HVI
Ph
161
Scheme 66.
66. Ritter’s nickel-mediated radiofluorination
radiofluorination via oxidation of Ni(II)
Ni(II) with
with (poly)cationic
(poly)cationic
Scheme
3
3
161, possessing
possessing neutral
neutral heterocycle
heterocycle ligands.
ligands.
λλ -iodane 161,
5.4. Conclusions
Conclusions
5.4.
High valent
valent nickel
nickel catalysis,
catalysis, specifically
specifically via
via the
theNi(II)/Ni(IV)
Ni(II)/Ni(IV) redox
redox couple
couple is
is an
an emerging
emerging area
area
High
of
research
that
has
the
potential
to
offer
novel
and
powerful
reactivity.
The
continued
growth
and
of research that has the potential to offer novel and powerful reactivity. The continued growth and
maturation
of
this
area
will
rely
on
continued
efforts
to
understand
the
role
that
ligand
scaffold
and
maturation of this area will rely on continued efforts to understand the role that ligand scaffold
oxidant
can can
playplay
in the
oxidation
states
accessible,
asaswell
isolation and
and
and
oxidant
in the
oxidation
states
accessible,
wellasasstudies
studiesaimed
aimed at
at the
the isolation
characterization
of
these
high
oxidation
state
complexes.
Furthermore,
a
more
detailed
mechanistic
characterization of these high oxidation state complexes. Furthermore, a more detailed mechanistic
understanding of
of reported
reportedsynthetic
syntheticmethods
methodswill
willeducate
educatefurther
furtherreaction
reactiondevelopment.
development.
understanding
6. Copper
Copper
6.
6.1.
6.1. Introduction
Introduction
As
As recently
recently as
as the
the year
year 2000,
2000, reports
reports of
of isolable
isolable high-valent
high-valent organometallic
organometallic Cu(III)
Cu(III) species
species were
were
extremely
rare
(Scheme
67a)
[147–149]
and
little
was
known
about
the
potential
role
of
Cu(I)/Cu(III)
extremely rare (Scheme 67a) [147–149] and little was known about the potential role of Cu(I)/Cu(III)
cycles
cycles in
in catalysis.
catalysis. However,
However, significant
significantprogress
progresshas
hasbeen
beenmade
madein
inthis
this area
areaover
overthe
the last
last 15
15 years
years and
and
modern
(RI-NMR)
have
provided
clear
evidence
of
modernanalytical
analyticaltechniques
techniquessuch
suchasasrapid-injection
rapid-injectionNMR
NMR
(RI-NMR)
have
provided
clear
evidence
Cu(III)
intermediates
in
carbon-carbon,
carbon-halogen,
and
carbon-nitrogen
bond
forming
reactions
of Cu(III) intermediates in carbon-carbon, carbon-halogen, and carbon-nitrogen bond forming
(Scheme
[1]. Applications
of hypervalentofiodine
reagentsiodine
in this area
are scarce
however
one scarce
could
reactions67b)
(Scheme
67b) [1]. Applications
hypervalent
reagents
in this
area are
imagine
will imagine
be a fruitful
research
in the coming
In this
recentyears.
examples
of
howeverthat
onethis
could
thatarea
thisofwill
be a fruitful
area ofyears.
research
in section
the coming
In this
proposed
Cu(I)/Cu(III)
redox
cycles
involving
hypervalent
iodine
reagents
will
be
presented,
though
section recent examples of proposed Cu(I)/Cu(III) redox cycles involving hypervalent iodine reagents
the
mechanisms
ofunderlying
these transformations
thetransformations
subject of debate
thethe
literature.
willunderlying
be presented,
though the
mechanismsare
ofstill
these
areinstill
subject of
debate in the literature.
Molecules 2017, 22, 780
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44 of 54
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44 of 54
a.
a.
EtO
EtO
C F
C66F 55
Me
Me
S
S
S
S
CuIII
CuIII
CF
CF33
CF
CF 33
N
N
Burton (1989)
Burton (1989)
C F
C66F 55
N
N
C F
C66F 55
CuIII
CuIII
N
N
Cl
Cl
N
N
N CuIIIIII
N CuS N
S N
S
S
S
S
NH
NH
C F
C66F 55
Santo (2006)
Santo (2006)
Osuka (2000)
Osuka (2000)
b.
b.
OTMS
OTMS CN
Li
CN
Li
CuIIIIII Me
Cu
Me
Me
Me
Me
Me
Conjugate addition
Conjugate addition
Me
Li
Me
Li
CuIIIIII Me
Cu Me
Me
Me
S 2 alklyation
S NN2 alklyation
Me
Me
Li
CuIII Me Li
CuIII Me
Me
Me
Me
Me
Me
Me
Br
Br
Me
CuIII Me
CuIII Me
Me
S 2 and S 2' allylic alklyation
S NN2 and S NN2' allylic alklyation
Br
HN Br CuIIIIII NH
HN
Cu NH
N
N
C–N, C–X, C–O
C–N, C–X, C–O
bond formation
bond formation
Scheme 67.
67. (a)
(a) Examples
Examples of
of isolable
isolable Cu(III)
Cu(III) complexes;
complexes; (b)
(b) Observed
Observed Cu(III)
Cu(III) species
species by
by rapid-injection
rapid-injection
Scheme
(RI) NMR
NMR spectroscopy.
spectroscopy.
(RI)
(RI)
NMR
spectroscopy.
6.2. Synthetic
Synthetic Applications
Applications
6.2.
Gaunt and
and co-workers
co-workers have
have reported
reported landmark
landmark examples
examples of
of Cu(I)/Cu(III)
Cu(I)/Cu(III) catalysis
catalysis through
through
Gaunt
reported
landmark
examples
of
Cu(I)/Cu(III)
C–H
arylation
of
indoles
and
benzene
derivatives
with
diaryliodonium
salts
(Scheme
68)
[150,151].
benzene derivatives
derivatives with
with diaryliodonium
diaryliodonium salts
salts (Scheme
(Scheme 68)
68) [150,151].
[150,151].
C–H arylation of indoles and benzene
Remarkably, these
these arylations
arylations proceeded
proceeded with
with extremely
extremely high
high
C3and
meta-selectivity
respectively,
Remarkably,
with
extremely
high C3C3- and
and meta-selectivity
meta-selectivity respectively,
respectively,
complimentary to
to the
the analogous
analogous Pd(II)-catalyzed
Pd(II)-catalyzed transformations
transformations which
which give
give exclusively
exclusively products
products
complimentary
transformations
complimentary
arising
from
directed
C–H
activation.
Shown
in
the
context
of
arene
functionalization
(Scheme
69),
Shown in
in the
the context
context of
of arene functionalization
functionalization (Scheme
(Scheme 69),
69),
arising from directed C–H activation. Shown
the authors
authors propose
propose aa catalytic
catalytic cycle
cycle
involving
Ph
2IBF4-mediated oxidation of Cu(I) to a highly
the
involving
Ph
IBF
-mediated
oxidation
of
Cu(I)
to
a
highly
cycle involving Ph22 44-mediated oxidation of Cu(I) to
electrophilic Cu(III)
Cu(III)
complex
163,
accompanied
byby
aryl
transfer.
This This
species
then then
undergoes
metaelectrophilic
Cu(III)complex
complex163,
163,accompanied
accompanied
aryl
transfer.
species
undergoes
electrophilic
by
aryl
transfer.
This
species
then
undergoes
metaselective
Friedel-Crafts-type
metalation,
facilitated
by
the
pendant
amide,
followed
by
rearomatization
to
meta-selective
Friedel-Crafts-type
metalation,
facilitated
by amide,
the pendant
followed by
selective
Friedel-Crafts-type
metalation,
facilitated by
the pendant
followedamide,
by rearomatization
to
give Cu(III)
Cu(III) complex
complex
164.
C–C
bond forming
forming
reductive
elimination
would
provide
the provide
desired
rearomatization
to give164.
Cu(III)
complex
164. C–Creductive
bond forming
reductivewould
elimination
would
give
C–C
bond
elimination
provide
the
desired
arylated
product
and
regenerate
Cu(I)OTf.
While
this
mechanism
explains
the
observed
selectivity,
the desired
arylated
and Cu(I)OTf.
regenerateWhile
Cu(I)OTf.
While this mechanism
theselectivity,
observed
arylated
product
andproduct
regenerate
this mechanism
explains theexplains
observed
the
intermediacy
of
Cu(III)
in
these
processes
has
not
been
confirmed
experimentally.
The
authors
selectivity,
the
intermediacy
of
Cu(III)
in
these
processes
has
not
been
confirmed
experimentally.
the intermediacy of Cu(III) in these processes has not been confirmed experimentally. The authors
note
that
the
addition
of
a
radical
inhibitor,
1,1-diphenylethylene,
does
not
inhibit
product
formation,
The authors
note thatofthe
addition
of a radical
inhibitor, 1,1-diphenylethylene,
does not
inhibit
note
that the addition
a radical
inhibitor,
1,1-diphenylethylene,
does not inhibit product
formation,
suggesting
radical
mechanism
is unlikely.
unlikely.
In contrast,
contrast,
Buchwald
has shown
shown
that Cu(I)-catalyzed
Cu(I)-catalyzed
product
formation,
suggesting
a radical
mechanism
is unlikely.
In contrast,
Buchwald
has shown that
suggesting
aa radical
mechanism
is
In
Buchwald
has
that
processes involving
involving
Togni’s
reagent Togni’s
proceedreagent
via one-electron
one-electron
radical
cascadesradical
[152]. cascades [152].
Cu(I)-catalyzed
processes
involving
proceed via
one-electron
processes
Togni’s
reagent
proceed
via
radical
cascades
[152].
Previous Reports
Previous Reports
N
N
H
H
Ph
Ph
Gaunt (2009)
Gaunt (2009)
Pd(II) catalysis
Pd(II)
I(BF )
Ph catalysis
Ph 22I(BF 44)
N
N
H
H
tBu
tBu
R
R
O
O
Ph
Ph
10 mol% Cu(OTf)
10 mol%
Cu(OTf)
Ph I(OTf)
Ph 22I(OTf)
74%
74%
NH
NH
Pd(II) Catalysis
Pd(II)
I(PF )
Ph Catalysis
Ph 22I(PF 66)
Me
Me
HN
HN
Gaunt (2009)
Gaunt (2009)
O
HN
O 10 mol% Cu(OTf)
HN
Me
10 mol%
Cu(OTf)
Ph I(BF )
Me
Ph 22I(BF 44)
79%
79%
Ph
Ph
N
N
H
H
tBu
tBu
O
O
Ph
Ph
Scheme 68.
68. Copper-catalyzed
Copper-catalyzed oxidative
oxidative arylation
arylation reactions
reactions with
with diaryliodonium
diaryliodonium salts
salts show
show
Scheme
Scheme
68.
Copper-catalyzed
oxidative
arylation
reactions
with
diaryliodonium
salts
show
complimentary regioselectivity
regioselectivity to
to analogous
analogous palladium-catalyzed
palladium-catalyzed systems.
systems.
complimentary
complimentary regioselectivity to analogous palladium-catalyzed systems.
Molecules 2017, 22, 780
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Me
H
N
tBu
O
Ph 2I(BF 4)
CuI(OTf)
Ph
PhI
Me
[PhCuIII(OTf)]BF 4
NH
TfO
CuIII
Ph
O
Me
tBu
NH
164
tBu
Me
O
HOTf
N
OTf
TfO
CuIII H O
H
tBu
Ph
163
Scheme 69.
69. Proposed
Proposed Cu(I)/Cu(III)
Cu(I)/Cu(III) catalytic
Scheme
catalytic cycle
cycle for
for C–H
C–H functionalization
functionalization of
of benzene
benzene derivatives.
derivatives.
6.3. Conclusions
6.3. Conclusions
The past 15 years have provided critical experimental evidence for the intermediacy of Cu(III)
The past 15 years have provided critical experimental evidence for the intermediacy of Cu(III) in a
in a variety of catalytic transformations. Hypervalent iodine reagents have been applied in seminal
variety of catalytic transformations. Hypervalent iodine reagents have been applied in seminal reports
reports by Gaunt using diaryliodonium salts in C–H arylation, however experimental evidence
by Gaunt using diaryliodonium salts in C–H arylation, however experimental evidence supporting a
supporting a Cu(I)/Cu(III) pathway is still lacking. Therefore, while the potential of hypervalent
Cu(I)/Cu(III) pathway is still lacking. Therefore, while the potential of hypervalent iodine reagents in
iodine reagents in high-valent copper catalysis is immense, the continued development of this area
high-valent copper catalysis is immense, the continued development of this area will require a more
will require a more detailed mechanistic understanding of the pathways involved.
detailed mechanistic understanding of the pathways involved.
7. Miscellaneous
Metal Complexes
Complexes
7.
Miscellaneous High
High Valent
Valent Metal
In addition
In
addition to
to the
the applications
applications discussed
discussed thus
thus far,
far, hypervalent
hypervalent iodine
iodine reagents
reagents have
have been
been utilized
utilized
as oxidants
for aa wide
as
oxidants for
wide range
range of
of metals
metals less
less prevalent
prevalent in
in traditional
traditional catalysis.
catalysis. These
These include
include oxidations
oxidations
of Mo,
Mo, W,
V, Ce,
Ce, Ir,
Ir,Fe
Feand
and Rh,
Rh, with
with aa large
large focus
focus on
on high
high valent
valent complex
complex isolation
isolation but
but aa few
few recent
recent
of
W, V,
examples
also
include
catalytic
reaction
development.
In
this
area,
PhICl
2 and PhI(OAc)2 have been
examples also include catalytic reaction development. In this area, PhICl2 and PhI(OAc)2 have been
the most
most widely
widelyapplied
applieddue
duetototheir
theirwell-studied
well-studied
reactivity
their
inherent
transfer
of chloride
the
reactivity
andand
their
inherent
transfer
of chloride
and
and
acetate
ligands
capable
of
stabilizing
high
oxidation
state
species.
acetate ligands capable of stabilizing high oxidation state species.
7.1. Complex Synthesis and Isolation
Scheme 70 summarizes the diverse metal complexes that have been accessed via hypervalent
hypervalent
oxidants.These
Thesecomplexes
complexesvary
vary
their
oxidation
states,
geometries,
ligand
scaffolds,
and
iodine oxidants.
in in
their
oxidation
states,
geometries,
ligand
scaffolds,
and were
were accessed
through
both and
one- two-electron
and two-electron
oxidation
pathways.
Filippou
utilized
PhICl
2 an
in
accessed
through
both oneoxidation
pathways.
Filippou
utilized
PhICl
in
2
an
oxidative
decarbonylation
approach
to
accessing
Mo(IV)
and
W(IV)
complexes
en
route
to
oxidative decarbonylation approach to accessing Mo(IV) and W(IV) complexes en route to studying
studying trichlorogermyl
compounds
[153]. Legzdins
synthesized
a V(II)complex
nitrosylusing
complex
using
trichlorogermyl
compounds
[153]. Legzdins
synthesized
a V(II) nitrosyl
PhICl
2 in
PhICl
2
in
order
to
study
the
nitrosyl
ligand
effects
on
early
transition
metals
[154].
In
an
effort
to
order to study the nitrosyl ligand effects on early transition metals [154]. In an effort to improve the
improve
the
syntheses
of
Ce(IV)
amides,
Andwander
and
Edelmann
synthesized
a
Ce(IV)
complex
syntheses of Ce(IV) amides, Andwander and Edelmann synthesized a Ce(IV) complex with use of
with use
PhICl2 as a oxidant
one-electron
[155].
Neve
2 to study
the
structureofand
PhICl
a one-electron
[155]. oxidant
Neve used
PhICl
studyPhICl
the structure
and
properties
an
2 as of
2 to used
properties
of
an
Ir(III)
dimer
[156].
A
report
from
Nocera
synthesized
Rh(III)
complexes
with
PhICl
Ir(III) dimer [156]. A report from Nocera synthesized Rh(III) complexes with PhICl2 as part of a study2
as understand
part of a study
understand
role of
Rh(III) hydride
complexesofinoxygen
the reduction
to
to
theto
role
of Rh(III) the
hydride
complexes
in the reduction
to H2 Oof
inoxygen
reactions
H2O HCl
in reactions
with HCl
[157]. Periana
demonstratedoffunctionalization
an both
Ir(V)PhI(OAc)
complex2with
with
[157]. Periana
demonstrated
functionalization
an Ir(V) complex of
with
and
both PhI(OAc)
and PhI(OTFA)
2 in order study oxy-functionalization
oxidation
PhI(OTFA)
study oxy-functionalization
reactions from highreactions
oxidationfrom
statehigh
iridium
[158].
2 in2order
state iridium
not
in Scheme
70,
PhI(OAc)
2 and
PhICl
2 also
have
rich
histories
Although
not [158].
shownAlthough
in Scheme
70,shown
PhI(OAc)
and
PhICl
also
have
rich
histories
as
co-oxidants
in
the
2
2
as
co-oxidants
in
the
study
of
metalloporphyrins
[159–161].
study of metalloporphyrins [159–161].
Molecules 2017, 22, 780
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46 of 54
Me
Me
Me
Me Si
Me
Cl
M IV Cl
PMe 2
Si
Me
P
2
OC
PMe 3
II PMe 2
VPMe
Cl
M
ClIV Cl
2
NO
Me 2Cl
P
OC
PMe 3
Cl VII PMe 2
[M = Mo
Cl or W]
NO
ClCl
Filippou
Legzdins
(2002)
[M = Mo (1999)
or W]
PhICl 2
PhICl 2
Filippou (1999)
Legzdins (2002)
PhICl 2
PhICl 2
Cl
Ph 2P
PPh 2
Cl
Et 3P
CO CO
Cl III
III I2
Ph
Rh
I 2IrPIII IrPPh
Cl
Cl
Et 3P
Cl CO CO
PEt 3
Cl
III I
RhIII
I 2IrPIII IrPPh
Ph
2
CO
Cl
Cl
PEt 3
Cl
Neve
Nocera
Ph
PPh 2
2P (1993)
CO(2012)
PhICl 2
PhICl 2
Neve (1993)
Nocera (2012)
PhICl 2
PhICl 2
Not shown:
Oxidation of Mn, Cr, Fe, Ru porphyrins
Not shown:
by PhI(OAc)
2 and PhICl 2
Oxidation of Mn, Cr, Fe, Ru porphyrins
by PhI(OAc) 2 and PhICl 2
Me
Cl
(TMS) 2N
(TMS) 2N
Cl IV
Ce
N(TMS)
2
CeIVN(TMS)
N(TMS)
2
2
N(TMS) 2
Andwander/Edelmann (2010)
PhICl 2
Andwander/Edelmann (2010)
PhICl 2
Ph
N
Ph
N
N
N
IrIII
N
N
tBu
IrIII
N
X
X
X
X
N
tBu
tBu
Periana (2007)
tBu
PhI(OAc) 2 or PhI(OTFA)
2
Periana (2007)
PhI(OAc) 2 or PhI(OTFA) 2
Scheme 70. Examples of high oxidation state transition metal complexes accessed by oxidation with
Scheme 70. Examples of high oxidation state transition metal complexes accessed by oxidation with
PhI(OAc)
2 and
PhICl2. of high oxidation state transition metal complexes accessed by oxidation with
Scheme 70.
Examples
PhI(OAc)
2 and PhICl2 .
PhI(OAc)2 and PhICl2.
7.2. Catalytic Applications
7.2. Catalytic Applications
7.2. Catalytic
Applications
Although
one-electron manifolds are not prototypical of hypervalent iodine reagents,
Although
one-electron
manifolds
areserve
not prototypical
of hypervalent
iodine
reagents,
diaryliodonium
salts have been
reported to
one-electron of
oxidants
in both iodine
iron
andreagents,
iridium
Although one-electron
manifolds
are not asprototypical
hypervalent
diaryliodonium
salts
have
been
reported
to
serve
as
one-electron
oxidants
in
both
iron
and
iridium
catalyzed
transformations.
catalysis
using
with Ph2I(BF
4) as iron
bothand
the external
diaryliodonium
salts have Photoredox
been reported
to serve
as Ir(III)(phpy)
one-electron3,oxidants
in both
iridium
catalyzed
transformations.
Photoredox
catalysis
using
, with 4Ph
)derivatives
asexternal
both the
2 I(BF
oxidant
and
phenyl source,Photoredox
was
successfully
applied
toIr(III)(phpy)
the Ir(III)(phpy)
methoxyphenylation
styrene
catalyzed
transformations.
catalysis
using
3, with3Ph2I(BFof
) as
both4the
external
oxidant
and
phenyl
source,
was
successfully
applied
to
the
methoxyphenylation
of
styrene
(Scheme
71) [162].
It is
proposed
Ph2I(BF4)applied
transfers
phenyl
radical to styreneof
with
in situ
oxidation
oxidant and
phenyl
source,
was that
successfully
toathe
methoxyphenylation
styrene
derivatives
+
+
derivatives
(Scheme
[162]. It 3that
is. proposed
Ph2to
I(BF
) transfers
atophenyl
radical
to styrene
with
of
Ir(III)(phpy)
3 to
Ir(IV)(phpy)
Further
a 4benzylic
cation
followed
byintrapping
with
(Scheme
71)
[162].
It71)
is proposed
Ph2I(BFoxidation
4) that
transfers
a phenyl
radical
styrene
with
situ
oxidation
+
+ Further oxidation to a benzylic cation followed
in methanol
situIr(III)(phpy)
oxidation
Ir(IV)(phpy)
gives3+of
the
difunctionalized
product.
3 . to
of
toIr(III)(phpy)
Ir(IV)(phpy)33+. to
Further
oxidation
a benzylic cation followed by trapping with
bymethanol
trapping gives
with methanol
gives the difunctionalized
product.
the difunctionalized
product.
1 mol% Ir(phpy) 3,
Ph 2I(BF 4)
1 mol% Ir(phpy) 3,
MeOH,
30 )W
Ph 2I(BF
bulb 4
MeOH,
30 W
42-83%
bulb
42-83%
R
R
OMe
OMe
Ph
Ph
R
R
Ph 2I(BF 4)
Ph 2I(BF 4)
IrIII(phpy)3+
IrIV(phpy) 3+
IrIII(phpy)3+
Ph
IrIV(phpy) 3+
hυ
Ph
hυ
IrIII(phpy)3
IrIII(phpy)3
MeOH
Ph
Ph
MeOH
Scheme 71. Ir(III)(phpy)3 catalyzed photoredox oxyarylation of styrene derivatives.
Scheme 71. Ir(III)(phpy)3 catalyzed photoredox oxyarylation of styrene derivatives.
Scheme
71. Ir(III)(phpy) catalyzed photoredox oxyarylation of styrene derivatives.
Loh has shown that Ph2I(OTf)3can act as a one-oxidant in an Fe(II)/Fe(III) catalyzed intramolecular
radical
cyclization
72)act
[163].
is proposedinthat
Ph2I(OTf) produces
a phenyl
radical
Loh
has showncascade
that Ph(Scheme
2I(OTf) can
as aItone-oxidant
an Fe(II)/Fe(III)
catalyzed
intramolecular
Lohoxidation
has
shown
Ph2to
I(OTf)
can72)
act[163].
as
a one-oxidant
inthat
an Fe(II)/Fe(III)
catalyzed
intramolecular
upon
ofthat
Fe(II)
Fe(III)
with
subsequent
hydrogen
abstraction
from
dichloromethane.
radical
cyclization
cascade
(Scheme
It is proposed
Ph
2I(OTf) produces
a phenyl
radical
radical
cyclization
cascade
(Scheme
72)
[163].
It
is
proposed
that
Ph
I(OTf)
produces
a
phenyl
radical
2
upon oxidation of Fe(II) to Fe(III) with subsequent hydrogen abstraction
from dichloromethane.
upon oxidation of Fe(II) to Fe(III) with subsequent hydrogen abstraction from dichloromethane.
Molecules 2017, 22, 780
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Molecules 2017, 22, 780
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Although these
these one-electron
one-electron pathways
pathways remain
remain rare,
rare, these
these reports
reports show
show promise
promise for
for the
the further
further
Although
development
of
hypervalent
iodine
reagents
in
these
manifolds.
development of hypervalent iodine reagents in these manifolds.
10 mol% FeCl 2,
Ph 2I(OTf)
O
N
Me
Me
CH 2Cl 2
80%
Me
CHCl 2
O
N
Me
Scheme
Scheme 72.
72. FeCl
FeCl22 catalyzed
catalyzed carbochloromethylation
carbochloromethylation of
of activated
activated alkenes.
alkenes.
7.3.
7.3. Conclusions
Conclusions
The
The versatility
versatility of
of hypervalent
hypervalent iodine
iodine reagents
reagents is
is evident
evident in
in the
the wide
wide range
range of
of metal
metal centers
centers that
that
they
they are
are capable
capable of
of oxidizing.
oxidizing. Their
Their application
application in
in the
the isolation
isolation and
and characterization
characterization of
of late
late transition
transition
metal
metal complexes
complexes provides
provides critical
critical insights
insights into
into the
the further
further development
development and
and application
application of
of these
these
species.
Furthermore,
their
ability
to
facilitate
one-electron
pathways
has
enabled
their
extension
species. Furthermore, their ability to facilitate one-electron pathways has enabled their extension into
into
metal
radical cascade
cascade reactions.
reactions.
metal catalyzed
catalyzed photoredox
photoredox and
and radical
8.
8. Conclusions
Conclusions
High
High valent
valent metal
metal catalysis
catalysis is
is still
still an
an emerging
emerging field
field that
that continues
continues to
to be
be rich
rich with
with opportunities
opportunities
for
novel
and
creative
reaction
development.
Hypervalent
iodine
reagents
have
emerged
for novel and creative reaction development. Hypervalent iodine reagents have emerged as
as versatile
versatile
oxidants
oxidants in
in this
this area,
area, providing
providing versatile
versatilereactivity,
reactivity, heteroatom
heteroatom ligands,
ligands, and
and mild
mildreaction
reactionconditions.
conditions.
These
also environmentally
environmentally benign,
These reagents
reagents are
are also
benign, non-toxic,
non-toxic, and
and relatively
relatively inexpensive
inexpensive compared
compared to
to
other
other inorganic
inorganic oxidants.
oxidants. Despite
Despite their
their broad
broad utility,
utility, there
there remain
remain limitations
limitations in
in their
their application;
application;
they
heteroatoms ligands
they produce
produce stoichiometric
stoichiometric organic
organic byproducts,
byproducts, there
there is
is aa limited
limited scope
scope of
of heteroatoms
ligands
available,
and
their
use
in
facilitating
challenging
reductive
eliminations
(i.e.,
available, and their use in facilitating challenging reductive eliminations (i.e., –CF
–CF33,, –F)
–F) is
is limited.
limited.
Future
Future developments
developments in
in more
more diverse
diverse hypervalent
hypervalent iodine
iodine scaffolds,
scaffolds, particularly
particularly in
in those
those that
that could
could
act
as
“innocent”
oxidants,
or
those
that
could
be
readily
recycled/regenerated,
has
the
potential
act as “innocent” oxidants, or those that could be readily recycled/regenerated, has the potential to
to
greatly
already powerful
powerful reaction
reaction manifold.
manifold.
greatly expand
expand the
the utility
utility of
of this
this already
Acknowledgments: The
University for
for their
their support.
support. Additionally,
The authors
authors would
would like
like to thank Temple University
Additionally,
acknowledgement isismade
thethe
donors
of the
Chemical
Society
Petroleum
Research
Fund forFund
support
madetoto
donors
of American
the American
Chemical
Society
Petroleum
Research
for
of
this
research.
support of this research.
Conflicts of Interest: The authors declare no conflict of interest.
Conflicts of Interest: The authors declare no conflict of interest.
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