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Direct Cross-Coupling Reaction of Simple Alkenes
with Acrylates Catalyzed by Palladium Catalyst
Yun-He Xu, Jun Lu, and Teck-Peng LohJ. Am. Chem. Soc., Article ASAP
Current LiteratureChenbo Wang @ Wipf GroupJan 17, 2009
Chenbo Wang @ Wipf Group Page 1 of 12 1/18/2009
Preparation of Diene Units with Cross-coupling Reactions: Classical Cross-coupling Reactions vs. Direct Cross-Coupling Reaction of Simple Alkenes
The challenge: •Chemoselectivity: dimerization•Stereoselectivity: cis/trans•Difficulty in activating alkene C-H without a directing group•Product stability
Chenbo Wang @ Wipf Group Page 2 of 12 1/18/2009
Construction of Diene Units in Natural Product Synthesis: Suzuki Reaction
O
OOMOM
BrBF3K
OBn
OH
O
OH O OMOM
BnOPd(PPh3)4,Cs2CO3THF/H2O42%
O
OH O OH
HN
ONOMe
Oximidine II
OOMOM
O
O
Ph OOMOM
O
Ph OOMOM
O
Ph
Br
Br
Br
PPh3, CBr4; Bu3SnH, Pd(PPh3)4;88%
O
OOMOM
Br
OBn
OH1. 2,5-dimethylhexa-2,4-diene, BH3.DMS, THF,2. H2O, then aq. CH2O,3. KHF2, acetone, MeCN, H2O; 99%
Molander, G. A. et al J. Am. Chem. Soc., 2004, 126, 10313
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Construction of Diene Units in Natural Product Synthesis: Negishi Reaction
Panek, S. J. et al J. Am. Chem. Soc. 2002, 124, 11368
Chenbo Wang @ Wipf Group Page 4 of 12 1/18/2009
Construction of Diene Units in Natural Product Synthesis: Stille and Heck Reaction
OMe
HO
O
ONH
HO
OI
I OMe
TBSO
OMe
OMeNH
TIPSO
O
OO
OMe
TBSO
OMe
OMeNH
TIPSO
O
CrCl2, CHI3;70%
1. Pd(MeCN)2Cl2, DMF/THF2. CAN, THF/H2O3. HF, CH3CN;
54% over 3 steps
SnBu3Bu3Sn
C8H17
HH
O O
O
(+)-mycotrienol
Intermediate in the total synthesis of taxol
C8H17
HH
O O
O
OTf
MeO C8H17
HH
O O
O
O
OMe1. KHMDS, PhNTf2; 90%2. TsOH, actone/H2O; 80%3. Ph3PCH3Br, KOtBu; 95%
Pd(PPh3)4, K2CO3, MeCN; 50%
Panek, J. S. et al J. Am. Chem. Soc. 1998, 120, 4123Danishefsky, S. J. et al J. Am. Chem. Soc., 1996, 118, 2843
Chenbo Wang @ Wipf Group Page 5 of 12 1/18/2009
Alkene Dimerization Reaction: Previous Work
Ishii, Y. et al Org. Lett. 2004, 6, 4623 and references therein
Kohll, C. F. and Van Helden, R. Recl. Trav. Chim. Pays-Bas 1967, 86, 1930
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The First Practical Example of Oxidative Alkene-alkene Oxidative Coupling
Ishii, Y. et al Org. Lett. 2004, 6, 4623
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Proposed Mechanism for Oxidative Alkene-alkene Oxidative Coupling
Chenbo Wang @ Wipf Group Page 8 of 12 1/18/2009
Direct Cross-Coupling Reaction of Simple Alkeneswith Acrylates: Optimization of Reaction Conditions
Chenbo Wang @ Wipf Group Page 9 of 12 1/18/2009
Direct Cross-Coupling Reaction of Simple Alkeneswith Acrylates: Substrate Scope
Suitable substratefor this methodology:
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Direct Cross-Coupling Reaction of Simple Alkeneswith Acrylates: Proposed Mechanism
Chenbo Wang @ Wipf Group Page 11 of 12 1/18/2009
Summary
• First example of direct cross-coupling reaction of simple alkenes with acrylates was reported.
• This methodology is still at early exploratory stage. Substrate scope is very limited.
• Future work: mechanistic study, a directing group for alkene C-H activation, milder conditions.
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