Light-Driven Enantioselective Acylation of Benzylic C–H Bonds Using Thiamine-Dependent Enzymes

Keywords

radical coupling - Breslow intermediate - acylation

Significance

Lu and co-workers report a photobiocatalytic enantioselective benzylic C(sp³)–H acylation using thiamine diphosphate dependent enzymes and a HAT catalyst. This method directly couples benzylic C–H bonds with aldehydes to form enantioenriched ketones under mild, anaerobic conditions. Mechanistic studies reveal that radical intermediates derived from enzyme-bound Breslow species and C–H substrates participate in the reaction, with the active site of the enzyme controlling stereoselectivity through radical–radical coupling.

 

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Comment

Traditionally, enantioselective C(sp³)–H acylation has required prefunctionalized reagents or proximity-driven activation strategies, often lacking generality and enantiocontrol. This biocatalytic platform presents a valuable alternative by enabling asymmetric C–C bond formation via direct, intermolecular C–H activation using native enzymes reprogrammed for non-natural reactivity. However, the system currently suffers from relatively low catalytic efficiencies.

 

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Publication History

Article published online:
23 July 2025