Catalyst- and Base-Free Asymmetric Synthesis of Functionalized Prolines via One-Pot Cascade Reactions

Abstract

A one pot, three-step cascade reaction to provide functionalized proline derivatives was developed. The Michael addition reaction of N-allylated proline and activated alkyne forms a zwitterionic intermediate that further undergoes cyclization and [2,3]-rearrangement to provide Cα-alkylated proline bicyclic derivatives. This transformation was highly stereoselective and the chirality of the N-allylated prolines was completely transferred to the product via a C−N−C chirality transfer process. The developed reaction is operationally simple and does not require any reagents other than the substrates. (Figure presented.).