Conformational Flexibility as a Tool for Enabling Site-Selective Functionalization of Unactivated <i>sp</i>^<i>3</i> C–O Bonds in Cyclic Acetals

Abstract

A dual catalytic manifold that enables site-selective functionalization of unactivated <i>sp</i>^<i>3</i> C-O bonds in cyclic acetals with aryl and alkyl halides is reported. The reaction is triggered by an appropriate σ*-p orbital overlap prior to <i>sp</i>^<i>3</i> C-O cleavage, thus highlighting the importance of conformational flexibility in both reactivity and site selectivity. The protocol is characterized by its excellent chemoselectivity profile, thus offering new vistas for activating strong <i>σ sp</i>^<i>3</i> C-O linkages.