Scope and Mechanism of the Ruthenium-Catalyzed sp³ C–H Coupling Reaction of 2-Alkylindoles with Enones for the Synthesis of Carbazole Derivatives

Authors

Krishna Prasad Gnyawali, Marquette University
Mina Son, Korea Advanced Institute of Science & Technology
Donghun Hwang, Korea Advanced Institute of Science & Technology
Nuwan Asanka Pannilawithana, Marquette University
Mu-Hyun Baik, Korea Advanced Institute of Science & Technology
Chase S. Yi, Marquette UniversityFollow

Document Type

Article

Publication Date

2025

Publisher

American Chemical Society

Source Publication

Organometallics

Source ISSN

0276-7333

Original Item ID

DOI: 10.1021/acs.organomet.4c00470

Abstract

The catalytic system consisting of a cationic Ru–H complex 1 and 3,4,5,6-tetrachloro-1,2-benzoquinone (L1) was found to be highly effective for the dehydrative sp³ C–H coupling reaction of 2-alkyl substituted indoles with enones to form 2,4-disubstituted carbazole products. The analogous coupling reaction of 2-alkylindoles with linear enones bearing the cyclic olefinic group afforded tetracyclic carbazole products. A normal deuterium kinetic isotope effect was measured from the coupling reaction of 1,2-dimethylindole versus 1-methyl-2-(methyl-d₃)indole with (E)-3-penten-2-one (k_H/k_D = 2.5). The Hammett plot was constructed from the reaction of para-substituted indoles 5-X-1,2-dimethylindole (X = OMe, Me, H, F, and Cl) with 4-phenyl-3-buten-2-one (ρ = −1.6 ± 0.2). The density functional theory (DFT) calculations were performed to obtain a complete energy profile for the coupling reaction. The combined experimental and DFT computational data revealed a detailed mechanistic path that features an initial coupling of indole and enone substrates, the turnover-limiting heterolytic sp³ C–H activation step, and the subsequent cyclization and dehydration steps. The catalytic method provides an efficient synthesis of carbazole derivatives from the dehydrative sp³ C–H coupling reaction of readily available indole with enone substrates without employing any reactive reagents or forming wasteful byproducts.

Comments

Accepted version. Organometallics, Vol. 44, No. 1 (January 13, 2025): 1-362. DOI. © 2025 American Chemical Society. Used with permission.

Recommended Citation

Gnyawali, Krishna Prasad; Son, Mina; Hwang, Donghun; Pannilawithana, Nuwan Asanka; Baik, Mu-Hyun; and Yi, Chase S., "Scope and Mechanism of the Ruthenium-Catalyzed sp³ C–H Coupling Reaction of 2-Alkylindoles with Enones for the Synthesis of Carbazole Derivatives" (2025). Chemistry Faculty Research and Publications. 1095.
https://epublications.marquette.edu/chem_fac/1095