Recent advances in theoretical studies on transition-metal-catalyzed regioselective C-H functionalization of indoles.

Indole compounds are widely found in natural products and drug candidates. The transition-metal-catalyzed regioselective C-H bond functionalization of indoles as the most efficient method for the synthesis of various functionalized indoles has been extensively studied in the past two decades due to its advantages of step economy and atom economy. In general, the catalysts included the transition-metals (Pd, Rh, Ru, Cu, Co, Fe, Zn, and Ga) and these reactions were accomplished with a remarkably wide range of coupling reagents for construction of various C-C and C-X (X = N, O, S) bonds. However, the general and important rules of the regioselectivity are not clear to date. Therefore, a comprehensive analysis through previous reported theoretical studies on transition-metal-catalyzed regioselective C-H bond functionalization of indoles was crucial and significant. In this review, we found that when the C-H bond activation process was the rate-determining step, the regioselectivity ordinarily occurred at the C7 or C4 positions (on benzene ring), and otherwise, the regioselectivity often occurred at C2 position (on pyrrole ring). For indoline substrates, the C-H bond functionalization occurred at the benzene ring. General rules of the regioselectivities for transition-metal-catalyzed C-H bond functionalization of indoles. This review collects major advances in the transition-metal-catalyzed C-H bond functionalization of indoles and indolines.