Iron-photocatalyzed Decarboxylative Oxygenation of Aliphatic Carboxylic Acids

Abstract Carboxylic acids, a bench-stable, readily available, and structurally diverse class of compounds, represent the ideal starting materials for organic synthesis. In this article, we highlight an iron-catalyzed decarboxylative C(sp3)−O bond-forming reaction that takes place under mild, photocatalytic, base-free conditions, using 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) derivatives as oxygenation reagents. The reaction is enabled by the ability of iron complexes to generate carbon-centered radicals directly from carboxylic acids through a sequence involving the photoinduced carboxylate-to-iron charge transfer, homolysis, and loss of carbon dioxide. The developed transformation displays exquisite substrate tolerance and was applied to various bio-active molecules. We performed an extensive mechanistic investigation via kinetic studies, electrochemistry, EPR, UV/Vis, HRMS, and DFT analysis. Those studies suggest that TEMPO plays three different roles in the reaction: it acts as an oxygenation reagent, serves as an oxidant to regenerate the Fe catalyst, and functions as an internal base for carboxylic acid deprotonation. The resulting TEMPO adducts are versatile synthons, which can be subsequently utilized in C−C and C−heteroatom bond-forming reactions employing commercially available organo-photocatalysts and nucleophilic reagents.

Publication History

Received: 14 October 2024

Accepted after revision: 17 December 2024

Accepted Manuscript online:
17 December 2024