Related Experiment Video
Updated: Sep 8, 2025

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
A directing group switch in copper-catalyzed electrophilic C-H amination/migratory annulation cascade: divergent
Hasina Mamataj Begam1, Shantanu Nandi1, Ranjan Jana1
1Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology 4 Raja S. C. Mullick Road, Jadavpur Kolkata-700032 West Bengal India rjana@iicb.res.in.
Abstract:
We present here a copper-catalyzed electrophilic ortho C-H amination of protected naphthylamines with N-(benzoyloxy)amines, cyclization with the pendant amide, and carbon to nitrogen 1,2-directing group migration cascade to access N,N-disubstituted 2-benzimidazolinones. Remarkably, this highly atom-economic tandem reaction proceeds through a C-H and C-C bond cleavage and three new C-N bond formations in a single operation. Intriguingly, the reaction cascade was altered by the subtle tuning of the directing group from picolinamide to thiopicolinamide furnishing 2-heteroaryl-imidazoles via the extrusion of hydrogen sulfide. This strategy provided a series of benzimidazolones and benzimidazoles in moderate to high yields with low catalyst loading (66 substrates with yields up to 99%). From the control experiments, it was observed that after the C-H amination an incipient tetrahedral oxyanion or thiolate intermediate is formed via an intramolecular attack of the primary amine to the amide/thioamide carbonyl. It undergoes either a 1,2-pyridyl shift with the retention of the carbonyl moiety or H2S elimination for scaffold diversification. Remarkably, inspite of a positive influence of copper in the reaction outcome, from our preliminary investigations, the benzimidazolone product was obtained in good to moderate yields in two steps under metal-free conditions. The N-pyridyl moiety of the benzimidazolone was removed for further manipulation of the free NH group.
Related Concept Videos
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Diazonium Group Substitution: –OH and –H
Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
Nucleophilic Aromatic Substitution: Elimination–Addition
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H
Directing Effect of Substituents: meta-Directing Groups
![[DPEPhosbcpCu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59739.jpg&w=3840&q=50)
