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

Abstract

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.

Mechanistic insight into conjugated N–N bond cleavage by Rh(iii)-catalyzed redox-neutral C–H activation of pyrazolones

“…3, featuring no Rh(V) intermediate involved. Considering that the corresponding Rh(I) species with the electroneutral center in Lin's report 32 has comparable stability to the N-C bond formation precursor, we conjectured that the zwitterionic character in 5 may be a key factor resulting in the instability of 5 over II′. 3, II further undertakes a struc-tural rearrangement to afford a more flexible intermediate II′ by the dissociation of the weakly coordinated aryl moiety.…”

“…Then, the alkyne inserts into the Rh-C5 bond of 4 via TS4-II with an energy demand of 10.4 kcal mol −1 , leading to the formation of a seven-membered rhodacycle II. 32 The hydrogen atoms not participating in the reaction have been omitted for clarity. In Zhang's proposal (Scheme 2), the N-N bond cleavage is proposed to realize through a Rh(III) → Rh(V) transformation.…”

Cobalt(III)‐Catalyzed Redox‐Neutral Synthesis of Unprotected Indoles Featuring an N−N Bond Cleavage

“…[15,17] After formation of the catalytically active cobalt species A,the C À Hmetalation takes place to form the cobaltacycle B which presumably is additionally stabilized by the Boc group. [15,17] After formation of the catalytically active cobalt species A,the C À Hmetalation takes place to form the cobaltacycle B which presumably is additionally stabilized by the Boc group.…”

Computational Studies on Heteroatom-Assisted C–H Activation and Functionalisation at Group 8 and 9 Metal Centres

“…5). This Rh (OAc) 2 Cp*-catalysed reaction was studied by Chen and Lin who reported M06 (DCE) energetics with an additional D3 correction [38]. After deprotonation, the terminal NAc position acts as a directing group for a two-step C-H activation via In contrast to previous pathways, no Rh(V) species are invoked in this process, but rather a Rh(III)-Rh(I)-Rh(III) pathway is proposed.…”

“…Davies, Macgregor and co-workers have studied the Rh(OAc) 2 Cp*-catalysed oxidative coupling of 5-methyl-3-phenylpyrazole and 4-octyne with BP86(DCE) and Key stationary points on free energy profiles (kcal/mol) for the Rh(OAc) 2 Cp*-catalysed reaction of 2-acetyl-1-arylhydrazines with diphenylacetylene to give indoles [38]. Double arrows indicate that several steps are involved, with the energy of the highest transition state between the two minima indicated in square brackets BP86-D3(DCE) calculations (Fig.…”