Conformational Flexibility as a Tool for Enabling Site-Selective Functionalization of Unactivated sp 3 C-O Bonds in Cyclic Acetals.

A dual catalytic manifold that enables site-selective functionalization of unactivated sp 3 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 sp 3 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 σ sp 3 C-O linkages.