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Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization.

ABSTRACT: 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.

SUBMITTER: Clayman PD

PROVIDER: S-EPMC7778473 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization.

Clayman Phillip D PD Hyster Todd K TK

Journal of the American Chemical Society 20200903 37

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 a ...[more]

PMID: 32857506

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