Zwitterionic Acyl Anion Equivalents from Carboxylic Acids via Acylsulfonylhydrazides: A Practical Organocatalytic Umpolung

The development of mild and practical acyl anion equivalents remains a cornerstone challenge in modern organic synthesis, as traditional umpolung strategies often rely on moisture-sensitive reagents, strong bases, or specialized N-heterocyclic carbene catalysts. Here we report that readily available N,N-acylsulfonylhydrazides serve as efficient acyl anion surrogates under operationally simple organocatalytic conditions. Using DMAP as a nucleophilic catalyst, these stable hydrazide precursors readily provide acylation products of a wide range of carbon electrophiles, including aromatic and aliphatic aldehydes, activated ketones, olefins, and imines. Mechanistic investigations, supported by DFT calculations and HRMS analysis, reveal an unconventional pathway wherein DMAP adds to the acyldiazene intermediate, triggering nitrogen extrusion and generating a zwitterionic nucleophile. This dual role of DMAP in enhancing both the stability and nucleophilicity of the reactive species circumvents the hydroxycarbene rearrangement pathway, offering a practical and scalable alternative to existing acyl anion methodologies.