Download Polyvalent Iodine in Synthesis (more than just Dess

Polyvalent Iodine in Synthesis
(more than just Dess-Martin)
Matthew M. Kreilein
Wednesday, December 13th, 2006
General Notes:
+ A LOT older than I though originally.
+ PhICl2 was the first reported polyvalent iodine(III) compound
prepared in 1886 by Willgerodt in Germany. PhIO2 first iodine(V)
compound, Willgerodt in 1900.
+ Chemical properties similar to Hg(II), Tl(III), Pb(IV), without the
nastiness. Also similar to organometallics to a certain extent (ligand
exchange, reductive elimination, etc.)
+ Four most useful forms in organic chemistry are as follows:
N-X-L system
N = no. of valence electrons
X = heteroatom
L = no. of ligands
L
I
L
L
L I
L
8-I-2
10-I-3
iodanes
L
L
I
L
L
L L
L I
L L
10-I-4
12-I-5
periodanes
General Notes:
+ Further “classified” by number of carbon ligands. Number of carbon
ligands affects the reactivity
Derivatives of Iodine(III) with one carbon ligand:
Iodosylarenes - ArIO
Iodoaryl halides - ArIX2
[Bis(acyloxy)iodo]arenes - ArI(O2CR)2
Strong acid derivatives - ArIX2 (X = RSO3, ClO4, NO3, etc.)
Five-membered Iodine(III) heterocycles (benziodoxoles and benziodazoles)
Derivatives with I-N bonds (amidodanes, iminiodanes, azidoiodanes)
Derivatives with I-”element” bonds
Iodine(III) species with one sp3-carbon ligand
Derivatives of Iodine(III) with two carbon ligands:
Cyano-, alkynyl-, alkenyl-, aryl-, heteroaryl-, alkyl-, and fluroroalkyliodonium
salts
Iodonium ylides
Iodonium imides
Derivatives of Iodine(III) with three carbon ligands
Derivatives of Iodine(V):
Iodyl compounds
Benziodoxole Oxides (IBX, DMP)
Derivatives of Iodine(III) with one carbon ligand
Iodosyl arenes - ArIO
+ polymeric in solution with secondary I-O bonds
O
O
I
Ar
I
Ar
O
O
I
Ar
+ but some have been isolated as monomers (intramolecular stabilization):
SO2t-Bu
I
1. H2O2, Ac2O
2. KOH, H2O
O
O S
t-Bu
I O
+ PhIO reactions usually carried out with a catalyst (Lewis acid, hdroxylic solvent, and others) in
order to depolymerize.
+ PhIO can also be activated in solid state by pulverization (mortar/pestle) with natural clays,
cation-exchange clays, and HCl-activated silica gel
+ Can be used as a precursor to a TON of other iodine(III) reagents:
PhIO
+
PhIX2
2 TMS-X
X = Cl, OAc, OCOCF3, OTs
OTf, N3, CN, etc.
TMS-OSO2R + TMS-X
PhI(OSO2R)X
X = OAc, NHAc, NCO, CN
R = p-Tol, CF3, C4F9
Tf2O at 0 °C
Ph
TfO
Tf2O or TfOH at rt
1/2 SO3 -50 °C
I
Ph
I
OTf
OTf
OH
I
OTf
PhI+-OSO3Ph
SO3, 50 °C
I
Ph
O
I
O
O
I
O
S
O2
Ph
Iodosylbenzene - PhIO
+ α-methoxylation of silyl ketene acetals
+ oxidation of 10 alcohols to carboxylic acids, 20 alcohols to ketones, sulfides to
sulfoxides
+ reaction tolerant of several functional groups
R2
OTMS (PhIO) , MeOH
n
57-74%
OR3
R1
MeO
R2
R1
CO2R3
R
R1 = Ph, 4-Me-C6H4, 4-MeO-C6H4, 4-Cl-C6H4
R2 = H, Me; R3 = Me, Et
S
R1
(PhIO)n, 10 mol% CTAB
toluene:H2O (500:1)
89-100%
R
RCH2OH
I O
Ph
KBr
O
(PhIO)n (2.2 eq), KBr (1 eq)
H2O, rt, quant%
RCO2H
KBr
O -K +
Ph
R1
R, R1 = Ph, 2-Me-C6H4, 2-MeO-C6H4, Bn, Me, Et
OH
(PhIO)n (2.2 eq), KBr (0.2-1 eq)
H2O, rt, 76-92%
O
S
I
Br
OH
O
I
Ph
O
OH
H
PhI
H2O
In MeOH, PhIO converted to PhI(OMe)2, in water, PhIO converted to PhI(OH)2
+ Other oxidations can be accomplished (very substrate dependent), asymmetric
variants also know using chiral Cr, Mn(III), Ru(II)/(III) complexes
PhIO, dry CH2Cl2
rt, 3 d
RCH2NH2
RC N
H
N
N
Cr+
O
H
Ph
N
CO2H
H
N
O
Me
NO3CF3
F3C
H
PhIO, Ph3PO, MeCN, 0 °C
H
N
PhIO (2.2 eq)
CH3Cl, rt, 2 d
PhIO, H2O, rt, 4 h
O
Ph
Me
+ In concert with I2, initiates radical chemistry…
O
RHN
OH
I(III)/I2
O
O
RHN
O
NHR
O
O
O
O
HOCO
-1e
R
NH
R
N
O
HOCO
O
HOCO
O
O
O
O
Iodoaryl halides - PhIX2
+ Very powerful yet selective halogenating agents; however, they aren’t that widely
used due to…
- difficult preparation (unless you like working with XeF2, F2, HF/HgO, etc. for
example)
- instability - PhIF2 for example is VERY hygroscopic so using any aqueous
methods is VERY clunky, bromides are unstable to the point that they can’t
be isolated as individual compounds.
+ Sometimes though, may be the best way to go…
OTMS
R
PhS
PhIF2, CH2Cl2, 12 h, 0 °C
OBn
SCN
R
presumably via... PhI(SCN)2
O
Tol
O
PhICl2, Pb(SCN)2, CH2Cl2, 0 to 25 °C
O
PhS
OBn
F
Tol
F
I
F
O
PhS
OBn
O
O
F I
Ph+S
OBn
Ph+S
OBn
F-
H
F-
[Bis(acyloxy)iodo]arenes - ArI(O2CR)2
+ Probably the most well-known and well studied of the polyvalent iodine(III)
compounds
+ Two are commercially available…
- (diacetoxyiodo)benzene - DIB - PhI(OAc)2 - 100g ~$100
- [bis(trifluoroacetoxy)iodo]benzene - BTI - PhI(OCOCF3)2 - 50g ~$150
+ Also can be used to make a TRAINLOAD of other [bis(acyloxy)iodo]arenes (WAY
too many to partially list).
+ Attachment to make polymer-supported variations has also been detailed.
+ Most useful as an oxidant for alkenes, heteroatoms, oxidative halogenation,
phenols, phenolic ethers as well as a radical initiator at carbon, oxygen, and
nitrogen.
+ Quite LOW reactivity for the oxidation of alcohols to aldehydes and ketones.
Oxidation can be carried out under µw or with addition of TEMPO. Useful if you
need to oxidize another functional group with an alcohol or aldehyde present as
oxidations with ArI(O2CR)2 do not give overoxidation to the acid.
RR'CHOH
DIB, TEMPO (0.1 eq),
CH2Cl2, rt, 6 min-15 h
55-95%
RR'C=O
[Bis(acyloxy)iodo]arenes - ArI(O2CR)2
+ α-hydroxylation of enolizable carbonyls
O
R2
R1
O
O
O-K+
OAc
I Ph
OAc
Ph
Ph
MeO
O
-OMe
Ph OMe
OH
MeO
OH
OH
Ph
O-
-OMe
Ph
AcO I Ph
R2
R1
O
1. PhI(OAc)2
KOH/MeOH
2. hydrolysis
Ph
O
PhI(O2CCF3)2
CF3CO2H, MeCN
H2O, 30-94%
Ph
I
OMe
Ph
OAc
O
hydrolysis
Ph
18O
18OH
label ends up here
if 18O labelled acetophenone is used
+ several fragmentations and rearrangements catalyzed by DIB and BTI especially at
electron-deficient centers.
EtO
EtO
O
EtO
OH
O
O
Ph
DIB
EtO
R
EtO
O I
EtO
OAc
R
O
EtO
O
O
R
O
-OAc
EtO
EtO
O
EtO
R
R
OAc
+ Also possible to oxidize sulfides to thiosulfonic S-esters or to arylsulfinic esters.
+ Notable use in sulfur oxidation is formation of carbonyls from monothioacetals or
dithianes
Ar-SS-Ar
+
BTI
S
R1
CH2Cl2, rt
or
ROH, reflux
S
R2
O
X = S or O
ArS XR
depending on condition
O
DIB, acetone/H2O
rt, 1-3 min, 64-92%
O
R1
R2
+ oxidation of phenols can be carried out using both DIB and BTI
OH
O
R5
R1
R4
R2
BTI, MeCN, H2O
R5
R1
R4
R2
OH
R3
R3
O
OH
DIB, ROH
OMe
MeO
OR
“Strong acid Derivatives” - ArI(OH)X
+ Most common is [hydroxy(tosyloxy)iodo]benzene - PhI(OH)OTs - HTIB also called
“Koser’s Reagent”
+ The mesylate form of HTIB is also available PhI(OH)OMs as is the phosphoryl
PhI(OH)OPO(OR)2 and “nosyl” flavor PhI(OH)ONs
+ In solution, these tend to be fully dissociated into PhI+OH -OTs (for example).
+ Many uses for these, but the primary use is for the functionalization of carbonyl
compounds by addition of the X group to the α-carbon, which is VERY handy for
one step functionalization of carbonyls.
Boc
Boc
N
HO
N
OH
I Ph
OTs
Boc
O
PhI(OH)OTs
CH2Cl2, rt
17 h, 68%
Boc
N
O
Ph
I
OH
N
Boc
O
N
OTs
O
-OTs
I+ Ph
+ Functionalization of carbonyls in this manner can be followed by conversion to
other functional groups. Very handy and some are one-pot two-step processes.
O
HNIB, MeCN, reflux
then
R3OH or SmI2 or NaN3
R2
R
O
R2
R
X
X = OR3, I, or N3
+ Always looking for improvements though…
I(OAc)2
P
TsOH·H2O, CH3Cl
rt, 24 h
O
OH
CH3Cl, reflux, 16 h
R2
R
O
I(OH)OTs
P
R2
R
OTs
OMe
+
I+
Ph
R
OH
-OTs
O
-30 °C
“up to 30% ee”
Ph
OTs
+ Can also catalyze the Hofmann Rearrangement:
NH2
Br
NH2
Br
O
O
BTI, MeCN/H2O
rt, 24 h, 83%
OTf
I OTf
Ph
Ph
H
I
N
OTf
Br
O
NH2
Br
Br
N
C
O
“Two carbon ligand derivatives” - translation…salts R2I+ X+ These seem to have caught fire in a “random” manner.
+ No real set scale of stability, utility, etc. as it is all VERY dependent on the identity
of the R and X groups. For example, several X = CN variants decompose at rt in 25 min and explode when exposed to air; however, other X = CN types (mainly the
cyclic forms) are stable indefinately.
+ Probably the most important research being done on them (synthetic organic
chemist speaking) are couplings with palladium and other metals with amines,
benzotraizoles, amidoximes, organoboron compounds, organostannanes, silanes,
leads, zirconium compounds, phosphites, mercaptans, alcohols, allenes,
substituted α,β-enones, Grignards, alkenes, alkynes, etc.
Ph2I+
X-
+
Y
Pd(PPh3)2Cl2, CuI
K2CO3,, DMF/H2O
rt, 2-3 h, 65-99%
Ph
Y
+ “Nucleophilic” substitutions are also known as well
R
I+Ph
X-
Nu-
R
Nu
PhO2S
R
I+Ph BF4-
PhSO2Na
PhO2S
R
SO2Ph
Iodonium ylides and imides (R1=IR2 and ArI=NSO2R)
+ Again, getting a bit more attention.
+ Synthetically speaking, they have found application in epoxidations, aziridinations,
Wittig olefination, amidation, and heteroatom imidation.
+ Again, asymmetric variations have been explored somewhat.
R
AcO
Me
EtOLi
I(Ph)X
OEt
R
O
I(Ph)X
R
OO
O
R1CHO +
IPh
R
R1CH=NR2 +
R1
O
(EtO)2P
R
O
IPh
IPh
O
R
O
O
-EtOAc
R2
N
R1CHO +
R
AcO
I(Ph)X
Et3N, PPh3
MeOH, rt to 60 °C
O
R
R1
via conversion of iodonium ylide to phosphonium ylide
R
R1
PhINTs, CuOTf
MeCN, rt
Ar
O
(EtO)2P
Ts
N
NHTs
Ar
R1
R2
PhINTs
chiral Ru(III) or Mn(III)-porphyrin
R1
R2
up to 53% ee
t-Bu
t-Bu
S
t-Bu
t-Bu
PhINTs, Cu(I) or Cu(II)
S
NTs
IBX and DMP
+ Varied applications in synthesis. Usually, what one can do the other can too
(oxidize alcohols, C-H to C-OH, etc.)
+ One notable difference, IBX can oxidized diols to diketones or α-hydroxy ketones
where as DMP usually leads to cleavage of the C-C diol bond. This has been
studied by NMR and shown to result from the ability of the diol to bond twice with
the iodine in DMP but not IBX.
+ IBX has also been show oxidize carbonyl compounds to α,β−unsaturated and
cross-conjugated ketones.
O OH
I
O
AcO OAc
I OAc
O
O
O
2-idoxybenzoic acid (IBX)
Dess-Martin periodinane (DMP)
Does IBX go BOOM!?!?!
I don’t know 100%, but if I had heard of it happening, this is probably the LAST thing I’d do…
CAUTION Compound 1 was reported to be explosive by Meyer and more recently by J. B. Plumb and D. J. Harper, ICI
Pharmaceuticals Group, in Chemical and Engineering News to be explosive similar to trinitrotoluene. The ICI preparation
of 1, found to be explosive, had 43.5% iodine by elemental analysis (calculated 45.32% for 1) although none of the
samples of 1 prepared by our method had any unexpected decrease in the percentage of iodine. They also had some
bromine (4%) in 1 after washing with only water. We washed with water and ethanol to form a nonexplosive sample of 1.
Although we have been unable to induce an explosion of 1 that would break the glass container or an explosion
upon hard impact of a steel hammer, we suggest that the synthesis of 1 be handled with care. It is possible that
some bromate or other impurity may be included in the samples found to be explosive
Dess and Martin, JACS, 1991, 113, 7277-7287
The Bottom Line (if there is one)
+ Polyvalent iodine compounds are more than just DMP
+ Have a wide array of synthetic utility
+ Drawbacks seem to be the need to prepare and instability of some of the reagents
in storage
Leading References
Stang, P.J.; Zhdankin, V.V. Chem. Rev. 1996, 96, 1123-1178 (564 references cited)
Zhdankin, V.V.; Stang, P.J. Chem. Rev. 2002, 102, 2523-2584 (690 references cited)