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

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 alpha-carbons can efficiently control the regioselectivity of the reaction by lone pair-cation interactions or steric hindrance reversing the main product preference, whereas cation-pi interactions are not so effective.

Automated summary

This study explores the competitive formation of isomeric bridged lactams via acid-catalyzed intramolecular Schmidt reactions from 3-azidoethylcyclopentanones using density functional theory (DFT) calculations. The results indicate that specific substituents at alpha-carbons can efficiently control the reaction's regioselectivity through lone pair-cation interactions or steric hindrance, while cation-pi interactions are less effective.