Physics

Stereocenter

Organic chemistry

Enzyme

Combinatorial chemistry

Reagent

Active site

Stereochemistry

Hypervalent molecule

Electron transfer

Enantioselective synthesis

Catalysis

Excited state

Photoexcitation

Intermolecular force

Alkene

Nuclear physics

Chemistry

Molecule

Flavin group

Photochemistry

Journal of the American Chemical Society

Intermolecular C–C bond-forming reactions are underdeveloped transformations in the field of biocatalysis. Here we report a photoenzymatic intermolecular hydroalkylation of olefins catalyzed by flavin-dependent 'ene'-reductases. Radical initiation occurs via photoexcitation of a rare high-order enzyme-templated charge-transfer complex that forms between an alkene, α-chloroamide, and flavin hydroquinone. This unique mechanism ensures that radical formation only occurs when both substrates are present within the protein active site. This active site can control the radical terminating hydrogen atom transfer, enabling the synthesis of enantioenriched γ-stereogenic amides. This work highlights the potential for photoenzymatic catalysis to enable new biocatalytic transformations via previously unknown electron transfer mechanisms.

Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins