%0 Journal Article
%T A General Iron-Catalyzed Decarboxylative Oxygenation of Aliphatic Carboxylic Acids.
%A Denkler LM
%A Aladahalli Shekar M
%A Ngan TSJ
%A Wylie L
%A Abdullin D
%A Engeser M
%A Schnakenburg G
%A Hett T
%A Pilz FH
%A Kirchner B
%A Schiemann O
%A Kielb P
%A Bunescu A
%J Angew Chem Int Ed Engl
%V 63
%N 32
%D 2024 Aug 5
%M 38735849
%F 16.823
%R 10.1002/anie.202403292
%X We report an iron-catalyzed decarboxylative C(sp3)-O bond-forming reaction under mild, base-free conditions with visible light irradiation. The transformation uses readily available and structurally diverse carboxylic acids, iron photocatalyst, and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) derivatives as oxygenation reagents. The process exhibits a broad scope in acids possessing a wide range of stereoelectronic properties and functional groups. The developed reaction was applied to late-stage oxygenation of a series of bio-active molecules. The reaction leverages the ability of iron complexes to generate carbon-centered radicals directly from carboxylic acids by photoinduced carboxylate-to-iron charge transfer. Kinetic, electrochemical, EPR, UV/Vis, HRMS, and DFT studies revealed that TEMPO has a triple role in the reaction: as an oxygenation reagent, an oxidant to turn over the Fe-catalyst, and an internal base for the carboxylic acid deprotonation. The obtained TEMPO adducts represent versatile synthetic intermediates that were further engaged in C-C and C-heteroatom bond-forming reactions using commercial organo-photocatalysts and nucleophilic reagents.