Enantioselective Three-Step Synthesis of Homo-β-proline: A Donor–Acceptor Cyclopropane as Key Intermediate

Abstract

An enantioselective three-step synthesis of the GABA uptake inhibitor ( S )-(+)-homo-β-proline was developed. The basis for the synthesis was the enantioselective Cu I -catalyzed cyclopropanation of N -Boc-pyrrole, a substrate that persistently has proved to be challenging in such transformations. The cyclopropanation can be performed on a 150 mmol scale, and the two subsequent steps (i.e., hydrogenation and in situ cyclopropane-opening/double-deprotection) toward the target molecule proceed smoothly in quantitative yield without loss of enantiopurity.