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.