Stereoselectivity in Cyclopropanation of Amino Acid-derived Enones

Abstract

An efficient synthesis of cyclopropyl peptidomimetics was developed by Dunlap et. al.; the key step of this synthesis is the cyclopropanation of amino-acid derived enones to access both nitrocyclopropyl and estercyclopropyl peptidomimetics. However, the key cyclopropanation step suffers from a lack of stereoselectivity. The goal of this study is to improve stereoselectivity in the cyclopropanation step using Gaunt's quinine and quinidine-based catalysts. Prior work using Gaunt's quinine methyl ether catalyst has shown improved diastereoselectivity for the syn isomer of some amino acids. Current efforts to improve diastereoselectivity using Gaunt's quinine and quinidine benzyl ether catalysts are reported here. The catalysts are selective for opposing diastereomers and improve diastereoselectivity for a wider range of amino acids.