Direct visible-light-excited flavoproteins for redox-neutral asymmetric radical hydroarylation

State-of-the-art non-natural photoenzymatic catalysis typically relies on either ultraviolet light activation or the formation of electron donor–acceptor complexes. Inspired by nature, herein we develop a biocatalytic scheme based on direct visible-light excitation of flavoprotein to achieve stereocontrolled intermolecular radical hydroarylation of alkenes with electron-rich arenes. Following visible-light activation, flavin-dependent ene-reductases—which naturally catalyse the two-electron reduction of activated alkenes—are repurposed to trigger single-electron oxidation of arenes and afford C( sp 2 )–C( sp 3 ) bond-forming products in a redox-neutral and enantiodivergent fashion while both enantiomers are obtained with different enzymes. Experiments and computational simulations demonstrate that the reaction is initiated from the single-electron oxidation of substrate by the direct visible-light-excited flavoprotein, and explain the origin of enantioselectivity in this radical hydroarylation that is otherwise notoriously challenging to achieve by chemocatalysis. This work expands the repertoire of photoenzymatic catalysis and will stimulate the development of further biotransformations.