Download Nickel-Catalyzed Cycloadditions

Nickel-Catalyzed Cycloadditions
Tristan Lambert
MacMillan Group Meeting
January 31, 2001
Properties of nickel
Introduction to metal-catalyzed cycloadditions
Nickel-catalyzed cycloadditions
Review of metal-catalyzed cycloadditions: Lautens, Chem. Rev., 1996, 96, 49.
Physical Properties of Nickel
Across the first row of transition metals, there is a trend towards decreased stability of higher oxidation states such that only Ni(II)
occurs in the normal chemistry of the element
Sc Ti V Cr Mn Fe Co Ni Cu Zn
decreased stability of
higher oxidation states
Cotton, Advanced Inorganic Chemistry, 6th ed.; p. 835
The vast majority of Ni(II) complexes are square planar
dx2-y2
Tetrahedral Ni complexes are important with bulky
(i.e. phosphine) ligands
dxy
"Free ion"
dz2
Tetrahedral
Octahedral
Tetragonal
distortion
Square planar configuration avoids occupation of high energy anitbonding orbital
dxz, dyz
Square
planar
Greenwood, Chemistry of the elements; p. 1347
Introduction to Metal-Catalyzed Cycloadditions
Definition of Cycloaddition:
-A reaction of two separate ! systems in which a ring is formed with two more " bonds and two fewer ! bonds
than the reactants
X
cycloaddition
cyclization
Note: As an exception to the above definition, in certain cases one of the ! systems can be a reactive " bond
Cycloadditions have been promoted by heat, light, Lewis acids, high pressure, and sonication
Many of these conditions require the presence of polarized functional groups in the substrate to facilitate the transformation. In
general reaction of unactivated olefins, acetylenes, or dienes is notoriously poor and extreme conditions are necessary to achieve
good yields of cycloadducts
Metal catalysts provide new opportunities for highly selective cycloaddition reactions since complexation of a metal to a reactant
significantly modifies its reactivity, thus allowing for improved reactivity and novel chemistry
It should be emphasized that while the products of these reactions are clearly cycloadducts, most if not all reactions proceed in
a stepwise fashion and probably involve a cyclization as a key event
Lautens, Chem. Rev., 1996, 96, 49.
[2 + 1] Cycloadditions: Ni(II) Catalyzed Cyclopropanations of Electron Deficient Olefins
Metal-Stabilized Alkyl Carbenes
Yield
(with respect
to CH2Br2)
10 mol% NiBr2
0.6 eq NaI, 0.8 eq Zn
CN
CN
92%
0.5 eq CH2Br2, 0 oC, 42h
10 mol% NiBr2
1.0 eq NaI, 0.8 eq Zn
CO2Me
CO2Me
10 mol% NiBr2
Me
1.0 eq NaI, 0.8 eq Zn
Me
O
90%
0.5 eq CH2Br2, 0 oC, 24h
97%
O
0.5 eq CH2Br2, 0 oC, 96h
Kanai, Chem. Lett., 1979, 1979.
Kanai, Bull. Chem. Soc. Jpn., 1983, 53, 1025.
General Reactivity Trends with Various Catalysts
catalyst
reactive olefins
Rh2(OAc)4
styrene, enol ethers
Cu(acac)2, CuClP(OMe)3
enamines, alkyl substituted olefins
Cu(OTf)2, Cu(OTf), Cu(BF4)2
terminal olefins
Pd(OAc)2, PdCl2, Pd(PPh3)4
styrene, strained, conjugated terminal olefins;
#,$-unsaturated carbonyl compounds
Ni(COD)2, Ni(PPh3)4, NaI/Zn and NiBr2
#,$-unsaturated carbonyl compounds, acrylonitrile
Catalytic Cycle of Ni(II) Catalyzed Cyclopropanation
Catalytic Cycle
NiBr2
Zn
EWG
Notes:
Differences with the Simmons-Smith reaction
ZnBr2
H
EWG
1. Electron deficient olefins are more
reactive than electron rich olefins
Ni0
2. Dibromomethane is more suitable than
diiodomethane
3. No cyclopropanation occurs in diethyl ether
(reactions performed in THF)
CH2Br2
EWG
Ni
10-20 mol% ZnBr2 or AlCl3 additive dramatically
increases yields. >50 mol% dramatically decreases
yields. Excess NaI (4 eq) is also beneficical.
Br
H
H2C
Ni
EWG
Br
EWG
The role of Lewis acids and solvent has not been
H
H
clarified
Zn or Ni0
Ni
EWG
ZnBr2 or NiII
EWG = CO2Me, CN, COMe, CHO
Kanai, Bull. Chem. Soc. Jpn., 1983, 53, 1025.
[2 + 1] Cycloadditions: Nickel Carbenes From Highly Strained Hydrocarbons
Bicyclo[1.1.0]butane: strain energy 66 kcal/mol
+
Ni(COD)2
CO2Me
CO2Me
0 oC
92%
H
Noyori, Tetrahedron Lett., 1974, 1749.
Mechanism:
R
R
H
R
Ni(0)
E
H
LnNi
E
H
Ni
H
H
R
LnNi
H
Nature of bonding in Ni-carbene
R1
Ni
H
R
H
Reaction is stereospecific with respect to the starting olefin
C
E
+
+
H
Ni
H
H
E
H
+
Ni
C
R2
-
E
R1
C
R2
Carbenoids involving metals with high backbonding capacity have considerable ylide character
Nickel has low electronegativity
carbenenoid carbon nucleophilic
Noyori, Tetrahedron Lett., 1973, 1691.
[2 + 1] Cycloadditions: Vinyl Carbenes
E
E
Me
MeO2C
73%
Me
A
CO2Me
Ni(COD)2
E
E
+
3% A
60%
MeO2C
B
CO2Me
Cis maleate undergoes Ni-catalyzed isomerization leading to small amounts of trans product
Mechanism:
E
E
E
E
Ln-1Ni
Ln-1Ni
E
Me
LnNi
not observed
E
Ln-1Ni
Me
E
Ln-1Ni
Ln-1Ni
E
E
E
Binger, Chem. Ber., 117, 1984, 1551.
[2 + 2] Cycloadditions: Catalysis of Thermally Forbidden Processes
Early Examples
Dimerization of Norbornadiene
Ni, Fe, or Co
cat.
Vallerino, J. Chem. Soc., 1957, 2287.
Dimerization of 1,3-butadiene
Ni(COD)2
+
P(O-o-biPh)3
97%
2.4%
Heimbach, ACIEE, 1967, 6, 800.
[2 + 2] Cycloadditions: Strained Alkenes and Electron Deficient Olefins
50 mol% Ni cat.
+
H
Z
45-70 oC
neat
72-120 h
A
Ni cat. = Ni(COD)2 or Ni(AN)2
Z = CN
55%
63:37
Z = CO2Me
72%
78:22
+
Z
Z
H
B
Yield
AN = acrylonitrile
A:B
Noyori, Bull. Chem. Soc. Jpn., 55, 1982, 852.
Ni(0) catalyzed reaction of electron deficient olefins with norbornadienes usually gives [2 + 2 + 2] homo-Diels-Alder adducts
Certain strained or highly reactive enophiles undergo exclusive [2 + 2] pathway
H
H
5 mol% Ni(COD)2
5.5 mol% PPh3
+
PhH, r.t., 24 h
Ni
86%
L
Note: Pd(0) results in [3 + 2] cycloaddition
Z
Noyori, J. Am. Chem. Soc., 1973, 95, 1674.
origins of endo selectivity
O
22 mol% Ni(COD)2
E
+
E
N
Ph
E
E
43 mol% PPh3
E = CO2Me
O
When E = electron donating
O
N
O
Ph
49%
exo only
endo products observed (5-12 : 1)
Lautens, J. Am. Chem. Soc., 117, 1995, 10276.
[ 2 + 2 ] Cycloadditions: Electron-Deficient Allenes
Thermal [ 2 + 2 ] with allenes gives mixture of regioisomers
R
R
R
heat
R
+
+
+
•
2
R
R
R
R
etc.
R
Nickel-catalyzed reaction is highly selective
EWG
EWG
EWG
2
•
cat. Ni0
•
-15 oC to rt
30 min to 3h
•
33-81%
single isomer
EWG
EWG
EWG = n-C6F13, C6F5, CO2Et, CON(Me)Ph, COEt, COPh, SO2Ph
Catalytic cycle
EWG
EWG
Ni0
•
EWG
EWG
EWG
•
Ni
Ni
•
EWG
EWG
Yamamoto, J. Am. Chem. Soc., 2000, 122, 10776.
[32! + 22" ] Cycloadditions: Metallocyclobutanes
Z
H
Z
H
D
Z
Z
Ni(AN)2
A
B
13%
87%
D
Z
D
+
H
D
H
H
D
Z
H
D
Z
Z
H
Z
H
(AN)2 = bisacrylonitrile
H
+
Z
D
H
H
H
H
D
D
H
C
+
Z
D
D
5%
61%
+
A
B
Z
4%
30%
Mechanism:
Z
NiLn
Ln
NiLn
Z
Z
Ni
Z
#-hydride elimination
Indicated bond in SM has one of the highest strain
energies known (47.4 kcal/mol)
Z
Z
Noyori, J. Am. Chem. Soc., 96, 1974, 634.
[32! + 22" ] Cycloadditions: Methylenecyclopropane
1.33D
D
D
D
+
EtO2C
Ni(an)2
CO2Et
0.08D
1.34D
1.34D
+
PhH, 60 oC
D
EtO2C
CO2Et
38
2D
CO2Et
62
Two possible pathways
Noyori, Tetrahedron Lett., 1978, 4823.
distal
attack
X
Y
"Naked" nickel catalysts such as Ni(COD)2
favor proximal ring opening
X
Y
M
1
3
CO2Et
2D
Phosphine ligands result in a preference for
distal ring opening
2
proximal
attack
X
Y
Palladium reacts exclusively at the distal
position
M
Y
X
Binger, Top. Curr. Chem., 1987, 135, 77.
Mechanism (proximal attack):
1
LnNi
E
E
3
1
3
E
3
1
LnNi
E
LnNi
E
E
E
E
Binger, Top. Curr. Chem., 1983, 116, 1.
Intramolecular [ 32! + 22" ] Cycloadditions With Methylenecyclopropanes
Synthesis of 13-Acetoxymodhephane
Me
M
CO2Me
AcO
CO2Me
Me
13-Acetoxymodhephane
MeO2C
catalyst (20 mol%)
temp.
yield
Ni(COD)2, PPh3
110 oC
74%
(PPh3)2PdCl2, DIBAL
130 oC
98%
Nakamura, J.Chem. Soc., Chem. Comm., 1988, 1112.
Selection of metal catalyst governs regiochemical product
Me
10 mol% Pd2(dba)3
Ni
40 mol% (iPrO)3P
PhMe, 110 oC
Me
Pd
MeO2C
CO2Me
CO2Me
CO2Me
59%
CO2Me
CO2Me
40 mol% Ni(COD)2
Me
PhMe, 0 oC
CO2Me
CO2Me
50%
CO2Me
Motherwell, Tetrahedron Lett., 1989, 7107.
[ 22" + 22" + 22" ] Cycloadditions: Alkyne Cyclotrimerizations
Although in principle thermal [ 2 + 2 + 2 ] cycloadditions are symmetry allowed, the entropic barriers associated with bringing
three reaction partners together and enthalpic activation energy contributions mitigate against such processes
The use of a transition metal catalyst enables entropic constraints to be circumvented by coordination of the reaction partners
to the metal complex in a stepwise process
R1
R2
metal catalyst
R3
R6
R1, R2
R5, R6
(Ni, Co, Pd, Cr, Rh, Fe, or Ta)
R3, R4
R4
R5
Intermolecular reaction suffers from chemo- and regioselectivity problems
R1
R
R
R
(Ni, Rh, or Co)
R2
R1
metal catalyst
+
( )n
complex product mixture
n = 2-5
( )n
R2
R
Partially intramolecular cyclotrimerization has become a very useful synthetic procedure
[ 22! + 22! + 22! ] Cyclotrimerizations: Mechanism and Scope
Modifications of Cyclotrimerization
General Mechanism:
R1
R2
R1
+
R3
R4
MLn
R4
R1
MLn-2
MLn-2
R4
R5
N
R5
R6
R5 N
C
N
R2
R6
C
MLn-2
R6
R4
O
Ln-2
M
R5
R3
R4
O
R3
R5
R2
C
R1
O
R3
R1
R6
O
R6
R4
R5 N
R6
N
R2
R1
R2
R2
R5
O
R5
R4
R3
O
R3
R3
N
R4
R4
R1
R6
R5 C
+
R5
R2
R5
R2
R3
R2
R3
R4
R1
R4
R5
R1
R5
R1
MLn-2
R3
R5
R6
R1
O
R1
R2
R3
N
R6
R6
R2
R3
R3
R4
R5
R5
R1
R1
R4
R2
R1
R3
R2
R2
R3
R2
R6
R4
N
O
R5
R4
Lautens,Chem. Rev., 96, 1996, 49.
[ 22! + 22! + 22! ] Cycloadditions: Semi-Intramolecular Alkyne Cyclotrimerizations
Asymmetric Synthesis of Isoindoline and Isoquinoline Derivatives
H
N
+
8 mol% Ni(COD)2
20 mol% L*
Tr
TMS
N
THF, 23 oC
TMS
H
TMS
TMS
Ph2P
L*
Yield
ee
(S, S)-BPPM
92%
60%
(R)-(S)-BPPFA
52%
73%
+
N
Tr
H
OtBu
Me
NMe2
PPh2
N
O
H
Tr
*
PPh2
Fe
(S, S)-BPPM
PPh2 (R)-(S)-BPPFA
8 mol% Ni(COD)2
40 mol% L*
THF,
N
*
23 oC
Tr
H
L*
Yield
ee
(S, S)-BPPM
42%
6%
(S)-MeO-MOP
62%
54%
OMe
PPh2
(S)-MeO-MOP
Mori, J. Org. Chem., 59, 1994, 6133.
[ 2 + 2 + 2 ] Cycloadditions: Alkynyl Enone / Alkene Cyclotrimerizations
Montgomery (w/ Jeongbeob Seo)
O
Ph
Ph
Ph
Ph
O
Ni(COD)2
or
O
O
Ph
PPh3
Ph
Ph
H
Ph
single stereoisomer from
either E or Z starting material
(99% and 63% yields respectively)
A
Reaction sets two rings and four contiguous stereocenters with complete stereoselectivity
Unusual chemoselectivity for alkene over alkyne in [ 2+ 2 + 2 ] cyclotrimerization
Simple enones
Me
Me
O
O
O
Ph
Ni(COD)2
Ph
O
Ph
PPh3
Ph
A
+
23%
H
75%
Me
Me
O
O
Ph
Me
O
Ni(COD)2
H
O
O
O
+
PPh3
Ph
H
Ph
68% combined
4 : 1 dr
H
Montgomery, J. Am. Chem. Soc., 1999, 121, 477.
[ 2 + 2 + 2 ] Cycloadditions: Alkynyl Enone / Alkene Cyclotrimerizations
Mechanism
O
O
R1
L
L
Ni
1
R2
R3
Ni(COD)2
R
R3
R1
H
PPh3
A
R1
O
L
Ni
R2
L
R3
H
O
O
R2
R1
R3
Ni(COD)2
L
B
L
Ni
R1
3
R
R1
H
PPh3
C
R4
O
Products to not isomerize or epimerize under
standard catalytic reaction conditions
R4
metallacycles and a kinetic preference for
addition of B or C to the simple enone to explain
R1
R4
L
O
Authors propose preequilibrium between nickel
O
Ni
R2
L
R3
H
R1
O
O
R2
H
R3
lack of reaction stereospecificity
Montgomery, J. Am. Chem. Soc., 1999, 121, 477.
[ 3 + 2 ] and [ 2 + 1 ] Cycloadditions: Diverse Reaction Manifolds From a Common
Nickel Metallocycle
O
O
R1
Ni0
R2
L
E
E+X-
R2
R2
H
E+X- = MeI,
RCHO, H2O
L
Ni
R1
OH
R1
Reaction conditions chemoselect for nickel enolate or vinyl nickel moiety
[ 3 + 2 ] adduct
R1
O
O
O2
H
L = TMEDA
R2
TMEDA suppresses [ 2 + 2 + 2 ] dimerization
[ 2 + 1 ] adduct
Montgomery, J. Am. Chem. Soc., 2000, 122, 6775.
Mechanisms
Ni
N
R1
N
N
O
O
R2
Ni N
R1
O
E+X-
X
Ni N
R1
E
R2
N
N
N
Ni
O
R1
R2
E
R2
O2
L + O
Ni
O
O-
R1
R2
R1
O
OL +
Ni O
R1
O
HO
E
O
R1
R2
R2
R2
[ 22! + 22! + 22! ] Homo-Diels-Alder Cycloadditions
First examples of Homo-Diels-Alder reaction
+
205 oC
O
O
O
H
O
Ullman,Chem. ind. (London)., 1958, 1173.
NC
CN
PhH
CN
reflux
+
NC
"small amount"
H
O
O
100%
CN
CN
Blomquist, J. Am. Chem. Soc., 1958, 81, 667.
CN
CN
Less activated olefins result in greatly diminished yields—acrylonitrile and norbornadiene (200 oC, 12h) gives only 12% yield
Nickel catalysts greatly broaden scope and efficiency of HDA
+
EWG
10% Ni(COD)2
20% PPh3
Cl
Cl
EWG
EWG
Temp.
Yield
exo : endo
COMe
80 oC
99%
>20 : 1
CHO
r.t.
58%
3:1
CN
80 oC
82%
4:1
SO2Ph
r.t.
75%
1:1
SOPh
r.t.
73%
a: P(OPh)3 used instead of PPh3
>19 : 1a
Lautens, J. Am. Chem. Soc., 1995, 117, 10276.
Norbornadienes: [ 2 + 2 + 2 ] Vs. [ 2 + 2 ]
Ni(COD)2
+
Y
X
Ni
PPh3
Y
Ni
Y
L
X
X
Highly electron-deficient olefins (e.g. N-phenylmaleimide) undergo [ 2 + 2 ] reaction
L
Y
L
Ni
Y
L
More electron-rich olefins (e.g. methyl vinyl
ketone) favor [ 2 + 2 + 2 ] pathway
X
X
Ni L
L
Reaction pathway appears to be dependent
upon coordination ability of the dienophile
X
Y
Y
X
[ 2 + 2 ] adduct
[ 2 + 2 + 2 ] adduct
Lautens, J. Am. Chem. Soc., 1995, 117, 10276.
[ 22! + 22! + 22! ] Homo-Diels-Alder Cycloadditions : Regio- and Stereoselectivity
2-Substituted Norbornadienes
13 mol% Ni(COD)2
24 mol% PPh3
MeO2C
+
Cl
Cl
MeO2C
94%
exo : endo = 2.3 : 1
, 80 oC
(para)
CN
CN
18 mol% Ni(COD)2
36 mol% PPh3
+
OMe
Cl
Cl
OMe
, 80
oC
(ortho) COMe
COMe
SiMe3
15 mol% Ni(COD)2
30 mol% P(OPh)3
+
Cl
CN
54%
(80% one isomer)
Cl
, 80 oC
SiMe3
(meta)
CN
47%
PPh3 gives mixture of
[2 + 2 + 2] and [2 + 2] adducts
Diene and dienophile substituents as well as ligands shown to have dramatic effect on selectivities
Lautens, J. Am. Chem. Soc., 1995, 117, 10276.
[ 22! + 22! + 22! ] Homo-Diels-Alder: Cyclic Vs. Acyclic Dienophiles
Acyclic Dienophiles: exo-selective
+
10 mol% Ni(COD)2
20 mol% PPh3
O
Me
Cl
Cl
, 80
99%
>20 : 1 exo : endo
oC
COMe
L
L
Ni
H
L
EWG
Ni
EWG
L
H
endo
disfavored
exo
favored
Cyclic Dienophiles: endo selective
10 mol% Ni(COD)2
20 mol% PPh3
56%
+
O
Cl
Cl
H
, 80 oC
H
endo only
O
H
L
H H
H
H
H
Ni
L
L
O
endo
favored
Ni H
L
O
exo
disfavored
Lautens, J. Am. Chem. Soc., 1995, 117, 10276.
[ 22! + 22! + 22! ] Homo-Diels-Alder: 7-Substituted Norbornadienes
R
R
R
+
20 mol% Ni(COD)2
40 mol% PPh3
+
Cl
Cl
, 80
A
MeOC
oC
COMe
R
B
R
COMe
+
C
MeOC
COMe
R
Yield
A:B:C:D
anti : syn
exo : endo
n-hexyl
83%
40 : 58 : 1.6 : 0.4
42 : 58
98 : 2
Ph
84%
54 : 45 : 0.8 : 0.2
55 : 45
99 : 1
Cl
60%
71 : 28 : 0.8 : 0.2
72 : 28
99 : 1
OCOPh
97%
80 : 20 : 0 : 0
80 : 20
100 : 0
OTIPS
90%
90 : 9 : 1 : 0
91 : 9
99 : 1
OMEM
89%
88 : 9 : 3 : 0
91 : 9
97 : 3
OtBu
95%
95 : 5 : 0 : 0
95 : 5
100 : 0
D
Anti : syn selectivity increases as group electronegativity of 7-substituent increases
Ab initio calculations indicate a shift of electron density from the anti-! olefin to the syn-! olefin as electronegativity increases
Lautens, J. Am. Chem. Soc., 1995, 117, 6863.
[ 44! + 22! ] Cycloadditions: Nickel-Catalyzed Diels-Alder Reactions
Reversal of thermal reactivity
Me
Me
135 oC
+
CO2Me
CO2Me
Me
Ni(acac)2, PPh3
Et3Al, 40
60%
Me
+
90%
CO2Me
oC
2:1
CO2Me
Garratt, J. Chem. Soc., Chem. Comm, 1974, 251.
Mechanism:
Ni0
+
NiII
Ni0
-Ni0
NiII
NiII
Wender, J. Am. Chem. Soc., 1989, 111, 6432.
[ 44! + 22! ] Cycloadditions: Nickel-Catalyzed Intramolecular Diels-Alder Reactions
Alkyne and Allene Dienophiles
Alkynes are typically poor dienophiles in the Diels-Alder reaction
OTBS
OTBS
10 mol% Ni(COD)2
Me
TMS
O
H
+
30 mol% P(o-biPh)3
25 oC, 11h
Me
OTBS
H
10 mol% Ni(COD)2
Me
>99%
2:1 dr
Me
H
H
Me
30 mol% P(o-biPh)3
25 oC, 11h
+
Me
O
TMS
TMS
O
98%
>99:1 dr
Wender, J. Am. Chem. Soc., 1989, 111, 6432.
Transition metal catalysts make these processes facile and synthetically useful
OMOM
Me
OTMS
3 steps
Me
TMSO
MeO
Steroidal,
20 mol% Ni(COD)2
Vitamin D derivatives
40 mol% P(OiC3HF6)3
C6H12, 80 oC
MeO
OMOM
90%
one diastereomer
Wender, J. Org.Chem., 1995, 60, 2962.
Allenes: Catalyst-controlled chemocomplementarity
H
Me
OTBS
OTBS
5 mol% [Rh(COD)Cl]2
OTBS
48 mol% P(O-o-BiPh)3
10 mol% Ni(COD)2
30 mol% P(O-o-BiPh)3
THF, 45 oC
THF, 25 oC
•
Me
H
Me
Wender, J. Am. Chem. Soc., 1995, 117, 1843.
[ 22! + 22! + 22! + 22! ] Cycloadditions: Cyclooctatetraene Synthesis
First example by Reppe, has been used on an industrial scale
Ni-Catalyst
4
CH(iPr)2
Ni
Ni-Catalyst = NiBr2 / CaC2, Ni(acac)2, Ni(COT)2
2
Reppe, Leibigs Ann. Chem., 1948, 560, 1.
CH(iPr)2
tom Dieck developed first method for regioselective cycloadditions with monosubstituted alkynes
R4
cat. (dad)2Ni
(dad)2Ni
R
major product
R
major product
R
R
R
CH2OH
R
R
R
R
CH2OTol
R
R
R
R
R
R
CH(CH3)OH
CH2CO2Me
R
R
R
R
tom Dieck, Chem. Ber., 1985, 118, 428.
[ 44! + 44! ] Cycloadditions: Cyclooctadiene Synthesis
Intermolecular
Substituted butadiene dimerization
X
10 mol% Ni(COD)2
X
benzene
Y
X, Y = OSiMe3 (18d)
90%
(24h)
70%
X, Y = CO2Me
Y
X = H, Y = CO2Me (72h)
33%
Waegell, Tetrahedron Lett. 1983, 24, 385.
Use of butadiene results in significant [ 4 + 2 ] adduct
Mechanism:
Ni
Ni
Ln
Ln
"1,"3-anti
bis-"1
H
NiLn
Ni
L
LnNi
NiLn
"3-bis
syn
Ni0
NiLn
NiLn
"3-bis anti
H
bis-"1
bis-"1
Conditions can be optimized to minimize vinylcyclohexene and divinylcyclobutane formation
Wilke, ACIEE, 1988, 27, 185.
[ 44! + 44! ] Cycloadditions: Intramolecular Cyclooctadiene Synthesis
3-atom tethers
cis-fused
H
11 mol% Ni(COD)2
33 mol% Ph3P
EtO2C
EtO2C
PhMe, 60
4-atom tethers
EtO2C
oC
70%
19 : 1 cis : trans
EtO2C
H
trans-fused
MeO2C
MeO2C
1:2
Ni(COD)2 : Ph3P
H
82%
5 : 95 cis : trans
H
Note: other substrates give much lower selectivities
Wender, J. Am. Chem. Soc., 1986, 108, 4678.
Type I
10 mol% Ni(COD)2
20 mol% Ph3P
Me
Me
92%
3 : 97 cis : trans
PhMe, 110 oC
MeO2C
MeO2C
H
Type II
20 mol% Ni(COD)2
40 mol% Ph3P
TBSO
52%
1.3 : 1 dr
TBSO
PhMe, 110 oC
Towards taxane skeleton
Wender, Tetrahedron Lett., 1987, 28, 2221.
[ 44! + 44! ] Cycloadditions: Enantioselective Total Synthesis of (+)-Asteriscanolide
Me
Me
1. isobutyric
anhydride
BrMg
CHO
1. LAH
2. Swern
2. LDA
68% (2 steps)
OH
57%
O
Darvon LAH
OH
red.
97%
98% ee
Me
Me
Me
3. Li
Me
4. Swern
CO2H
Me
Me
Me
Red-Al
Me
SnMe3Cl
83%
Me
64% (4 steps)
O
OH
SnMe3
SnMe3
OH
Me
+
Me
O
n-BuLi
•
CO2
Me
Me
PPh3, 90 oC
Me
56%
67%
Me
Me
O
O
O
Ni(COD)2
Me
Me
O
O
O
H
Red-Al
Me
CuBr
Me
74%
H
Me
H
Me
Me
BH3 THF
Me
PCC
Me
48%
H
Me
Wender, J. Am. Chem. Soc., 1988, 110, 5904.
H
H
O
Me
(+)-Asteriscanolide
[ 2 + 2 + 1 ] Cycloadditions: Cyclopentenone Synthesis
R
R3SiCN
cat. Ni(COD)2 / L2
R
X
R
H+
N
X
PhH, 8h
O
X
SiR3
Ph
Ph
L2 =
N
N
Ph
Ph
Representative examples
Ph
Ph
O
O
O
O
Ph
Me
60%
Ph
O
N
38%
2 : 1 dr
H
40%
Ph
Ph
O
O
41%
Me
O
O
EtO2C
O
EtO2C
H
70%
Me
58%
>98 : 2
Buchwald, J. Org. Chem., 1996, 61, 4498.
Nickel-Catalyzed "Zipper Annulation" of Conjugated Enynes
R
R
R
cat. Pd0
2
R
R
EWG
EWG
EWG
cat. Ni0
2
52-89%
PhMe, rt
EWG
EWG
EWG = n-C6F13, PhCF2, n-C6H13CF2
Catalytic cycle
Yamamoto, J. Am. Chem. Soc., 2000, 122, 1810.
EWG
EWG
Ni
Ni
or
EWG
Ni
Ni0
EWG
EWG
EWG
EWG
EWG
Ni
EWG