Stereoselective synthesis of Xaa-Yaa type (Z)-chloroalkene dipeptide isosteres via efficient utilization of organocopper reagents mediated allylic alkylation

Abstract

An efficient method for an atom-economical synthesis of Xaa-Yaa type (Z)-chloroalkene dipeptide isosteres (CADIs) in high yield and diastereoselectivity has been developed. Reaction of an allylic gem-dichloride compound with organocopper reagents prepared from catalyst quantity of 30 mol% CuCl and organozinc reagents causes formation of (Z)-chloroalkenes corresponding to (L,D)-type Xaa-Yaa CADIs by diastereoselective allyic alkylation. Using (E)-enoates of substrates in place of (Z)-enoates in similar reactions with organocopper reagents, which prepared from 140 mol% CuCl and organozinc reagents, provides various (L,L)-type CADIs.