Trichloromethyl Carbanion in Aqueous Micelles: Mechanistic Insights and Access to Carboxylic Acids from (Hetero)aryl Halides

While suppressing the decomposition of trichlor-omethyl carbanions (generated from CHCl3 using the LiOH base) to carbon monoxide and their participation in transmetallation and reductive elimination steps of cross-coupling's catalytic cycle, a micelle-enabled catalytic carboxylation of (hetero)aryl halides is developed. The aqueous micelles play a crucial role in stabilizing both the highly reactive trichloromethyl carbanion and the single-metal atom catalyst to facilitate the desired reaction pathway efficiently. Comprehensive mechanistic analyses, including kinetic studies in the presence of trichloromethyl carbanion or carbon monoxide, H/D exchange via trichloromethyl anion, and mass spectrometric analysis of reaction intermediates, support a carbanion pathway. Simultaneously, the scope of this method was demonstrated over 40 substrates signifying broad functional and protecting group tolerance. This methodology was applied to the synthesis of isotopically enriched carboxylic acids using simple 18OH2 and/or 13CHCl3-labeled precursors.

Automated summary

A micelle-enabled catalytic carboxylation of (hetero)aryl halides has been developed, utilizing aqueous micelles to stabilize reactive carbanions and single-metal atom catalysts. Mechanistic analyses support a carbanion pathway, and the method shows broad substrate tolerance and is applied to the synthesis of isotopically enriched carboxylic acids.