Hydrogen atom transfer carbonylation for aliphatic carboxylic acid derivative synthesis

Abstract

Aliphatic C-H bonds are ubiquitous in industrial feedstocks and natural molecules, and their direct carbonylation represents a fundamentally important strategy to access aliphatic carboxylic acid derivatives. Conventional carbonylation approaches typically rely on prefunctionalized substrates such as alkyl halides or alkenes. In contrast, hydrogen atom transfer (HAT)-enabled strategies allow direct C-H bond activation, providing a more atom-economical and step-efficient route for molecular skeleton construction. This approach leverages differences in C-H bond dissociation energies as well as the intrinsic reactivity of open-shell intermediates, proceeding through a cascade sequence of HAT, CO capture, and acyl species formation to forge key C-C(O) bonds. As such, HAT-mediated carbonylation represents a powerful strategy for the construction of aliphatic carboxylic acids and their derivatives and has demonstrated broad potential in the selective functionalization of inert C-H bonds. This review summarizes the early developments and the latest advances in HAT-mediated C-H carbonylation reactions, with a particular focus on the construction of aliphatic carbonyl compounds, especially carboxylic acid derivatives.