Metal-Free-Mediated C(sp3)–H Bond Functionalization via Oxidative Cross-Dehydrogenative Coupling

Abstract

The functionalization of C(sp³) –H bond through 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 C(sp³) –H bond at the benzylic position of inactivated 2-methylindoles promoted by simple reagent NCS or NBS associated with nitrogen-, oxygen-, sulfur-, and carbon-nucleophiles, via oxidative cross-dehydrogenative coupling strategy, forming C(sp³) –N, C(sp³) –O, C(sp³) –S, and C(sp³) –C bond. Different from our previous approaches, this methodology was demonstrated to be a robust protocol consisting of chlorination or bromination and then SN2′ nucleophilic substitution processes, and presents a reasonably broad substrate scope and excellent functional group tolerance, thus enabling the late-stage functionalization of complex drugs, amino acids and natural products.