Abstract: A highly effective synthetic route to produce donor-acceptor azetines through the highly enantioselective [3+1]-cycloaddition of silyl-protected enoldiazoacetates with aza-ylides using chiral copper(I) catalysis is provided. In one embodiment, the 2-azetidine cycloaddition products undergo generation of 3-azetidinones by reactions with nucleophiles that produce a broad spectrum of peptide products by the retro-Claisen reaction provided by facile strain with high efficacy and complete retention of enantiopurity. This ring opening reaction uncovers a new methodology for the attachment of chiral peptide units to a variety of amines and alcohols, and tolerates a broad scope of nucleophiles including naturally occurring amines, alcohols, amino acids, and other nitrogen based nucleophiles.

Abstract: A highly effective synthetic route to produce donor-acceptor azetines through the highly enantioselective [3+1]-cycloaddition of silyl-protected enoldiazoacetates with aza-ylides using chiral copper(I) catalysis is provided. In one embodiment, the 2-azetidine cycloaddition products undergo generation of 3-azetidinones by reactions with nucleophiles that produce a broad spectrum of peptide products by the retro-Claisen reaction provided by facile strain with high efficacy and complete retention of enantiopurity. This ring opening reaction uncovers a new methodology for the attachment of chiral peptide units to a variety of amines and alcohols, and tolerates a broad scope of nucleophiles including naturally occurring amines, alcohols, amino acids, and other nitrogen based nucleophiles.