Rhodium(III)-Catalyzed Hydrazine-Directed C–H Activation for Indole Synthesis: Mechanism and Role of Internal Oxidant Probed by DFT Studies

DFT calculations have been carried out to study the detailed mechanism of Rh­(III)-catalyzed C–H activation/cyclization of 2-acetyl-1-arylhydrazines with alkynes leading to the formation of indoles, in which the hydrazine moiety is used as the internal oxidant. The energy profiles associated with the catalytic cycle, involving N–H deprotonation, C–H activation (a concerted metalation–deprotonation (CMD) process), alkyne insertion, ring rearrangement/isomerization, and finally N–N bond cleavage/reductive elimination to regenerate the active species, are presented and analyzed. Through analysis of the calculation results, we found that the combined processes of the CMD and alkyne insertion contribute to the overall rate-determining step. The N–N bond cleavage step was examined in detail to understand how the internal oxidant interacts with the metal center to facilitate the catalytic reactions. The factor influencing regioselectivity was also investigated. How different types of substrates (alkynes versus alkenes) and internal oxidants (−NH­(NHAc) versus −NH­(OAc)) influence the reaction mechanisms, Rh­(III)/Rh­(I) versus Rh­(III)/Rh­(V) catalytic cycles, was discussed