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Photoenzymatic asymmetric incorporation of fluorinated motifs into olefins

Li, Maolin1; Yuan, Yujie1; Harrison, Wesley1; Zhang, Zhengyi1; Zhao, Huimin1

Published Jun 11, 2024 on Dryad. https://doi.org/10.5061/dryad.r2280gbm6

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Jun 11, 2024 version files 1.15 MB

Abstract

Enzymes capable of assimilating fluorinated feedstocks are scarce, which poses a challenge for the biosynthesis of fluorinated compounds used in pharmaceuticals, agrochemicals, and materials. We develop a photoenzymatic hydrofluoroalkylation that adeptly integrates fluorinated motifs into olefins. The photoinduced promiscuity of flavin-dependent ene-reductases enables generation of carbon-centered radicals from iodinated fluoroalkanes, which are directed by the photoenzyme to engage enantioselectively with olefins. This approach facilitates stereocontrol through interaction between a singular fluorinated unit and the enzyme, securing high enantioselectivity at β-, γ-, or δ-positions of fluorinated groups via enzymatic hydrogen atom transfer, a process notably challenging with conventional chemocatalysis. This work advances enzymatic strategies for integrating fluorinated chemical feedstocks and opens new avenues for asymmetric synthesis of fluorinated compounds.