J Am Chem Soc. 2011 Jan 12;133(1):115-22. doi: 10.1021/ja108795x. Epub 2010 Dec 10.

Radical and Heck cyclizations of diastereomeric o-haloanilide atropisomers.

Journal of the American Chemical Society

David B Guthrie, Steven J Geib, Dennis P Curran

PMID: 21142031 DOI: 10.1021/ja108795x

Abstract

The outcomes of radical cyclizations and Heck reactions of N-(cyclohex-2-enyl)-N-(2-iodophenyl)acetamides depend critically on the configurations of the chiral axis and the stereocenter. In substrates without an ortho-methyl group, the diastereomeric precursors interconvert slowly at ambient temperatures. Cyclization of enriched mixtures of diastereomers provided similar yields of acetyl tetrahydrocarbazoles or dihydrocarbazoles, suggesting that interconversion of the radical or organometallic intermediates also occurs. Diastereomers of N-(cyclohex-2-enyl)-N-(2-iodo-4,6-dimethylphenyl)acetamides with an additional ortho-methyl group did not interconvert at ambient temperatures and were readily resolved. In radical cyclizations, syn diastereomers were prone to cyclize, while anti isomers were not. Strikingly, Heck reactions gave the opposite result; anti isomers were prone to cyclization and syn isomers were not. Heck reactions of allylic acetates occur with β-hydride elimination when acetate is trans to palladium and with β-acetoxy elimination when acetate is cis. This is surprising because prior studies have suggested that a trans relationship of palladium and acetoxy is essential for acetate elimination. Analyses of the results provide insights into mechanisms for radical cyclization and for insertion and elimination in the Heck reaction.

Publication Types

• Journal Article