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DOI: 10.1055/a-2638-4081
Recent Advances in Photoinduced Ketyl and Ketyl-Type Radical Generation from Aldehyde Derivatives
We thank the University of Bristol, Syngenta, and the Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training in Technology Enhanced Chemical Synthesis (EP/S024107/1) for funding.
Abstract
Ketyl radical generation from carbonyls is an important strategy in organic synthesis that enables common electrophilic functional groups to be transformed into nucleophilic radicals. However, the large negative reduction potentials of carbonyls mean that direct conversion to ketyl radicals by single-electron reduction is challenging and requires strongly reducing conditions. As a result, alternative strategies to access these useful radical intermediates have been developed that circumvent traditional reductive pathways. For example, recent reports have demonstrated that aldehydes can be converted into various activated aldehyde derivatives that are readily transformed to ketyl radicals or protected ketyl (ketyl-type) radicals through mechanistically distinct pathways, including photoinduced single-electron oxidation and halogen atom transfer. Herein, we review the synthesis and applications of different aldehyde derivatives that have been developed to allow facile access to ketyl and ketyl-type radicals under mild visible-light photochemical conditions.
Keywords
Ketyl radicals - Ketyl-type radicals - Photocatalysis - Photoredox catalysis - Halogen atom transfer - Dual photoredox/nickel catalysisPublication History
Received: 01 May 2025
Accepted after revision: 16 June 2025
Accepted Manuscript online:
17 June 2025
Article published online:
30 July 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
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For selected examples of photoredox-catalyzed ketyl radical formation from aromatic aldehydes and ketones, see:
Visible-light photocatalyzed carbonyl–olefin couplings of aliphatic ketones have also been reported using excited state organic radicals as strong reductants. However, under these highly reducing conditions, ketyl radical formation may not occur due to the preferential reduction of the olefin substrate over the ketone:
During the revision of this manuscript, Shen and co-workers reported the extension of α-hydroxy silane-derived ketyl-type radicals to perfluoroalkyl aldehydes, which were used in enantioselective dual photoredox/Ni-catalyzed cross-couplings with aryl halides: