Substituent effects on intramolecular Schmidt reactions: a theoretical study on the formation of bridged lactams

Abstract

The competitive formation of isomeric bridged lactams via acid-catalyzed intramolecular Schmidt reactions from 3-azidoethylcyclopentanones is explored using density functional theory (DFT) calculations, primarily performed at the M06-2X/6-311++G(d,p) level of theory. The results indicate that specific substituents installed at α-carbons can efficiently control the regioselectivity of the reaction by lone pair–cation interactions or steric hindrance reversing the main product preference, whereas cation–π interactions are not so effective.