Stereoselective preparation of β,γ-methano-GABA derivatives

Abstract

The Kulinkovich–de Meijere reaction between an unsaturated Grignard reagent and a chiral amide takes place with a high trans stereoselectivity and provides a convenient access to non-racemic trans cyclopropylamines. These compounds are transformed in four steps into the corresponding N-protected β,γ-methano-GABA derivatives, which are obtained for the first time in enantiomerically pure form. The corresponding transformations of the cis cyclopropylamine adducts are also described.