Site-Selective Divergent C-H Halogenation of Carbazoles and Indolines

Abstract

Halogenated heterocycles are of paramount importance due to their pivotal role in drug discovery and materials science, which underpins the tremendous demand for precise halogenation methodologies. However, precise and divergent C-H halogenation of those compounds still faces the persistent challenges of selectivity and often requires harsh reaction conditions. Here, we developed efficient and practical strategies for the precise site-selective halogenation of carbazoles and indolines. Specifically, the C-3 bromination of carbazoles and C-5 bromination of indolines were achieved using TBATB as the brominating agent under mild and metal-free conditions. Concurrently, C-1,6 and C-3,6 dibromination of carbazoles can be proceeded in the absence of reductant in the mixed solvent of acetonitrile and water upon prolonging the reaction time and increasing the dosage of TBATB. The Pd catalyzed selective C-1 chlorination of carbazoles and C-7 chlorination of indolines were realized when employing CuCl2•2H2O both as chlorine source and oxidant. Furthermore, a metal-free protocol employing HBr as the bromine source successfully accomplished the selective C-5 bromination of indoles and C-3 bromination of carbazoles. The methods are characterized by its simple operation, good selectivity, broad substrate scope, mild reaction condition, scale up synthesis, product derivatization, and readily available starting materials.