Copper-catalyzed remote C(sp3)–H azidation and oxidative trifluoromethylation of benzohydrazides

摘要

The Hofmann-Löffler-Freytag (HLF) reaction is a prototypical example of radical-based remote functionalization of unactivated C(sp³)–H bond. While 1,5-hydrogen atom transfer (1,5-HAT) of the amidyl radical is thermodynamically favorable and is well-established, the method for the subsequent functionalization of the translocated carbon radical is still limited. We report herein two catalytic remote C(sp³)–H functionalization protocols. Cu(MeCN)4PF6-catalyzed reaction of 2-alkyl benzohydrazides >3 with TMSN3 in the presence of MeCO2OtBu affords the γ-azido amides >4, while CuCl-catalyzed reaction of >3 with Togni’s reagent provides 2-(β-trifluoromethylvinyl)benzamides >5 via an oxidative δ-trifluoromethylation of the alkyl group. Mechanistic studies suggest that the γ-azidation of benzohydrazides >3 goes through 1,5-HAT followed by a Cu-mediated azido transfer cascade, while the oxidative δ-trifluoromethylation of >3 proceeds via, after 1,5-HAT process, a radical-polar crossover mechanism.