Practical, metal-free remote heteroarylation of amides via unactivated C(sp3 )–H bond functionalization
Nana Tang‡a, Xinxin Wu‡a and Chen Zhu a ,b ,*（朱晨）
a Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, China.
b Key Laboratory of Synthesis Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Road, Shanghai 200032, China
‡ N. T. and X. W. contributed equally to this paper.
Chem. Sci., 2019, 10, 6915--6919
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.