A novel electrochemical Hofmann-type rearrangement enables facile access to α-oxoisocyanates for the synthesis of N-carbamoylacetamides†

Abstract

The utilization of amines as nucleophiles in Hofmann rearrangement remains a persistent challenge in the field of electrochemistry due to the small difference in oxidation potential between the commonly employed bromide catalysts and amines that would lead to amine deactivation. Herein, we demonstrate an unprecedented Hofmann-type rearrangement that allows convenient access to the challenging α-oxoisocyanates from readily available α-oxoamides with TBAI as the only additive under electrochemical conditions. A variety of primary and secondary amines were examined as effective coupling partners to afford value-added N-carbamoylacetamides with exceptional chemoselectivity and satisfactory yields. Besides, the protocol readily yields N-acylcarbamates with alcohol nucleophiles. This atom-/electron-economical, scalable method features operational simplicity, broad substrate scope, and excellent functional group tolerance. The potential utility of this strategy has been elucidated by its applicability in the concise synthesis of drugs and insecticides. The success of this electrochemical method stems from its unique mechanism to convert α-oxoamides into α-oxoisocyanates through the concerted efforts of TBAI catalysts and nucleophiles, rather than the direct amide activation commonly employed in traditional Hofmann rearrangement. Furthermore, the choice of TBAI and the cathodic reduction is crucial for the transformation.