Physics

Organic chemistry

Enzyme

Radical

Quenching (fluorescence)

Enantioselective synthesis

Catalysis

Nucleophile

Disproportionation

Chemistry

Semiquinone

Alkyl

Quantum mechanics

Radical disproportionation

Flavin group

Redox

Photochemistry

Fluorescence

Journal of the American Chemical Society

Flavin-dependent "ene"-reductases can generate stabilized alkyl radicals when irradiated with visible light; however, they are not known to form unstabilized radicals. Here, we report an enantioselective radical cyclization using alkyl iodides as precursors to unstabilized nucleophilic radicals. Evidence suggests this species is accessed by photoexcitation of a charge-transfer complex that forms between flavin and substrate within the protein active site. Stereoselective delivery of a hydrogen atom from the flavin semiquinone to the prochiral radical formed after cyclization provides high levels of enantioselectivity across a variety of substrates. Overall, this transformation demonstrates that photoenzymatic catalysis can address long-standing selectivity challenges in the radical literature.

Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization