Metal-free C(sp3)–H bond functionalization via oxidative cross-dehydrogenative coupling

Abstract

The functionalization of the C(sp³)–H bond through an oxidative cross-dehydrogenative coupling strategy represents a challenging transformation in the field of organic chemistry. In continuation of our research interest in green oxidation of indoles, herein we further explore the direct functionalization of the C(sp³)–H bond at the benzylic position of unactivated 2-methylindoles promoted by a simple reagent, NCS or NBS, associated with nitrogen, oxygen, sulfur, and carbon nucleophiles, via an oxidative cross-dehydrogenative coupling strategy, forming C(sp³)–N, C(sp³)–O, C(sp³)–S, and C(sp³)–C bonds. Different from our previous approaches, this methodology was demonstrated to be a robust protocol consisting of chlorination or bromination and then S_N2′ nucleophilic substitution processes, and exhibits a reasonably broad substrate scope and excellent functional group tolerance, thus enabling the late-stage functionalization of complex drugs, amino acids and natural products.