Work

Cu-Catalyzed Asymmetric Carbene Insertion into N–H, O–H, and S–H Bonds: Challenging the Existing Mechanistic Dogma

Year: 2025

Type: article

Abstract: A comprehensive mechanistic study of asymmetric carbene insertion into N-H, O-H, and S-H bonds catalyzed by Cu-spiroBox is presented. We challenge the currently widely accepted mechanism involving Cu-enolate intermediates that has dominated carbene insertion reactions for more than a decade. Our DFT and DLPNO-CCSD-(T) calculations show that in all cases, the preferred route involves metal-associated enol intermediates. Our study demonstrates that the tautomerization process is dependent on the nature of the nucleophile: O-H and S-H insertion follow a stepwise route, whereas N-H insertion adopts a concerted pathway. This step is also found to control the stereochemical outcome in all three cases. Our study highlights the importance of enol intermediates in carbene chemistry, which might be more prevalent than what is currently believed.

Source: JACS Au

DOI: 10.1021/jacsau.5c00807

Authors: Arushi Tyagi, Kriti Gupta, Garima Jindal

Institution: Indian Institute of Science Bangalore

Language: English

Topic: Cyclopropane Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $3,500

Funders: Indian Institute of Science, Council of Scientific and Industrial Research, India, Science and Engineering Research Board