Amide hemiaminals from retro-Claisen ring opening of chiral 2-siloxy-1-cyclobutene-1-carboxamides

Abstract

Nucleophilic retro-Claisen ring opening of chiral cis-3,4-disubstituted cyclobutene-1-carboxamides with amines forms cyclic hemiaminals in good yield with complete retention of configuration. The chiral cyclobutene-1-carboxamides are prepared by [3 + 1]-cycloaddition of donor-acceptor 2-silyloxy-1-cyclopropene-1-carboxamides by copper(I) catalysis with chiral SaBox ligands with high cis selectivity in modest yields and enantioselectivities. Retro-Claisen ring opening by benzylamine formed the cyclic hemiaminal as the dominant product, but ring opening by cyclohexylamine gave the open form as the dominant product. The cyclic hemiaminal and open form are not interconvertible under the reaction conditions.