A new enantioselective route to kainoids: application to the formal synthesis of (–)-α-kainic acid

Abstract

The enantioselective synthesis of a 2,3,4-trisubstituted pyrrolidine featuring the kainoid C-2, C-3 trans, C-3, C-4 cis arrangement of substituents has been accomplished through a tandem Michael reaction strategy involving 2-nitro-3-methylbuta-1,3-diene as electrophilic alkene, the removable electron-withdrawing group acting as a template for control of the stereochemistry of the cyclization, together with a secondary benzylamine incorporating a chiral centre at the carbon bearing the nitrogen nucleophile and an appropriate α,β-unsaturated acceptor able to trap the initially formed nitronate.