Copper-Catalyzed Alkylative Deoxygenation of O-Substituted Hydroxamic Acid Derivatives with Grignard Reagents: A Combined Experimental and Computational Study

TL;DR

This study explores a copper-catalyzed chemical reaction that forms amides using hydroxamic acid derivatives and Grignard reagents, combining experiments with computational analysis.

Contribution

The paper introduces a novel copper-catalyzed amidation mechanism involving electrophilic acyl nitrenoid intermediates.

Findings

CuCN catalyzes amidation via electrophilic acyl nitrenoid intermediates.

Magnesium salts play a key role in triggering the formation of these intermediates.

The study provides insights into the reactivity of organomagnesium cuprates.

Abstract

A mechanistically unusual CuCN-catalyzed electrophilic amidation of Grignard reagents with N-H containing O-allyl- and O-benzyl-hydroxamic acid derivatives as leaving groups to give secondary amides is reported. Computational DFT examination of the reaction points to the intermediate formation of electrophilic acyl nitrenoid species triggered by the presence of CuCN and magnesium salts. The work also provides some experimental evidence about the molecular composition and reactivity of organomagnesium cuprates, the structural nature of which remains a subject of ongoing debate.

Figures