Abstract
Carboxylic acids, a bench-stable, readily available, and structurally diverse class
of compounds, represent 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 a photoinduced
carboxylate-to-iron charge transfer, homolysis, and loss of carbon dioxide. The developed
transformation displays exquisite substrate tolerance and was applied to various bioactive
molecules. We performed an extensive mechanistic investigation through kinetic studies;
electrochemistry, EPR, UV/Vis, and HRMS analyses; and DFT calculations. 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 that can be subsequently utilized in C–C and C–heteroatom bond-forming reactions
employing commercially available organophotocatalysts and nucleophilic reagents.
1 Introduction
2 Background on the LMCT Reactivity of Iron Complexes
3 Direct Iron-Photocatalyzed Decarboxylative Oxygenation: Reaction Concept
4 Substrate Scope Assessment of Decarboxylative Oxygenation
5 Mechanistic Considerations
6 Conclusion
Key words
decarboxylation - oxygenation - photocatalysis - carboxylic acids - iron catalysis
- TEMPO
