Radical Termination via β-Scission Enables Photoenzymatic Allylic Alkylation Using “Ene”-Reductases

Allylations are practical transformations that forge C–C bonds while introducing an alkene for further chemical manipulations. Here, we report a photoenzymatic allylation of α-chloroamides with allyl silanes using flavin-dependent "ene"-reductases (EREDs). An engineered ERED can catalyze annulative allylic alkylation to prepare 5, 6, and 7-membered lactams with high levels of enantioselectivity. Ultrafast transient absorption spectroscopy indicates that radical termination occurs via β-scission of the silyl group to afford a silyl radical, a distinct mechanism by comparison to traditional radical allylations involving allyl silanes. Moreover, this represents an alternative strategy for radical termination using EREDs. This mechanism was applied to intermolecular couplings involving allyl sulfones and silyl enol ethers. Overall, this method highlights the opportunity for EREDs to catalyze radical termination strategies beyond hydrogen atom transfer.