Remote Nucleophilic Substitution at a C(sp3)-H Bond of α-Bromocarboxamides via 1,4-Hydrogen Atom Transfer To Access N-Acyl-N,O-acetal Compounds.

Abstract

Herein, we report a remote nucleophilic substitution reaction via 1,4-hydrogen atom transfer (1,4-HAT) to synthesize N-acyl-N,O-acetal moieties. α-Bromocarboxamide undergoes rSN at a C(sp3)-H bond in the presence of an alcohol/phenol and a copper catalyst. Mechanistic studies using deuterated α-bromocarboxamide confirmed that the 1,4-HAT process is the rate-determining step. Topologically complex N-acyl-N,O-acetal molecules can be accessed using our rSN reaction with various α-bromocarboxamides via chemoselective reactions.