Practical, metal-free remote heteroarylation of amides via unactivated C(sp3)–H bond functionalization

Abstract

Development of practical methods for the production of multi-functionalized amides is one of the most important topics in both synthetic chemistry and drug discovery. Disclosed herein is a new, efficient, site-selective heteroarylation of amides via C(sp³)–H bond functionalization. Amidyl radicals are directly generated from the amide N–H bonds under mild conditions, which trigger the subsequent 1,5-HAT process. A wide scope of aliphatic amides including carboxamides, sulfonamides, and phosphoramides are readily modified at remote C(sp³)–H bonds by installing diverse heteroaryl groups. Borne out of pragmatic consideration, this protocol can be used for the late-stage functionalization of amides.