Amphoteric Amino Aldehydes Reroute the Aza-Michael Reaction

Abstract

Amphoteric amino aldehydes, which exist as stable dimers, participate in an aza-Michael/aldol domino reaction with alpha,beta-unsaturated aldehydes to afford stable 1,5-aminohydroxyaldehydes in high yields and diastereoselectivies. The reaction outcome hinges upon the dimeric nature of amphoteric amino aldehydes and the orthogonality between the NH aziridine and the two aldehyde functionalities during the reaction. Through the use of reaction conditions that disfavor dimer dissociation, the aza-Michael process has been directed toward a novel 8-(enolendo)-exo-trig cyclization. The results described herein further demonstrate the potential of amphoteric molecules in reaction discovery.