Direct Cross-Coupling Reaction of Simple Alkenes with Acrylates Catalyzed by Palladium Catalyst

Yun-He Xu, Jun Lu, and Teck-Peng Loh J. Am. Chem. Soc., Article ASAP

Current Literature Chenbo Wang @ Wipf Group Jan 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 O O PPh ,CBr ; Bu3SnH, Pd(PPh3)4; OMOM 3 4 OMOM 88% OMOM Ph O Ph O Ph O Br O Br Br OBn OBn 1. 2,5-dimethylhexa-2,4-diene, BH3.DMS, THF, OH O 2. H2O, then aq. CH2O, OH O 3. KHF , acetone, MeCN, H O; 99% OMOM 2 2 OMOM O O

Br Br BF3K

H N BnO Pd(PPh3)4, Cs CO O 2 3 OMOM OH N THF/H2O OH O OH O 42% OMe O O

Oximidine II

Molander, G. A. et al J. Am. Chem. Soc., 2004, 126, 10313

Chenbo Wang @ Wipf Group Page 3 of 12 1/18/2009 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 Bu3Sn O OMe SnBu3 1. Pd(MeCN)2Cl2,DMF/THF 2. CAN, THF/H2O CrCl , CHI ; 3. HF, CH CN; NH 2 3 3 NH 70% NH 54% over 3 steps O OMe OMe TBSO HO O O TBSO O O I HO OMe TIPSO O OMe TIPSO I OMe (+)-mycotrienol

C H C H MeO OMe C8H17 8 17 8 17 1. KHMDS, PhNTf2;90% O 2. TsOH, actone/H2O; 80% OTf Pd(PPh3)4,K2CO3, MeCN; 50% 3. Ph3PCH3Br, KOtBu; 95% H H H H H H

OO OO OO

O O O

Intermediate in the total synthesis of taxol

Panek, J. S. et al J. Am. Chem. Soc. 1998, 120, 4123 Danishefsky, 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

Chenbo Wang @ Wipf Group Page 6 of 12 1/18/2009 The First Practical Example of Oxidative Alkene-alkene Oxidative Coupling

Ishii, Y. et al Org. Lett. 2004, 6, 4623

Chenbo Wang @ Wipf Group Page 7 of 12 1/18/2009 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 Alkenes with Acrylates: Optimization of Reaction Conditions

Chenbo Wang @ Wipf Group Page 9 of 12 1/18/2009 Direct Cross-Coupling Reaction of Simple Alkenes with Acrylates: Substrate Scope

Suitable substrate for this methodology:

Chenbo Wang @ Wipf Group Page 10 of 12 1/18/2009 Direct Cross-Coupling Reaction of Simple Alkenes with 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.

Chenbo Wang @ Wipf Group Page 12 of 12 1/18/2009