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. 2020 Jun 2;59(23):9143-9148.
doi: 10.1002/anie.202001824. Epub 2020 Mar 24.

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids

Anna V Bay  1 , Keegan P Fitzpatrick  1 , Rick C Betori  1 , Karl A Scheidt  1
Affiliations

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids

Anna V Bay et al. Angew Chem Int Ed Engl. .

Abstract

As a key element in the construction of complex organic scaffolds, the formation of C-C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various C-C bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids. Facile construction of the acyl azolium in situ followed by a radical-radical coupling was made possible merging N-heterocyclic carbene (NHC) and photoredox catalysis. The utility of this protocol in synthesis was showcased in the late-stage functionalization of a variety of pharmaceutical compounds. Preliminary investigations using chiral NHCs demonstrate that enantioselectivity can be achieved, showcasing the advantages of this protocol over alternative methodologies.

Keywords: N-heterocyclic carbenes; ketones; photochemistry; radicals; reaction mechanisms.

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Figures

Scheme 1.
Scheme 1.
Oxidations of the Breslow intermediate and expansion to one-electron reduction of acyl azoliums
Scheme 2.
Scheme 2.
Enantioselective reaction with a chiral NHC.
Scheme 3.
Scheme 3.
Mechanistic studies and proposed mechanism
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