Asymmetric photoenzymatic incorporation of fluorinated motifs into olefins

• 成果类型: Article
• 署名作者: Li, Maolin; Yuan, Yujie; Harrison, Wesley; Zhang, Zhengyi; Zhao, Huimin
• 署名单位: University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11192
• DOI: 10.1126/science.adk8464
• 发表日期: 2024-07-26
• 页码: 416-421
• 关键词: density functionals; ene-reductases; basis-sets; thermochemistry; state; wave

摘要

Enzymes capable of assimilating fluorinated feedstocks are scarce. This situation poses a challenge for the biosynthesis of fluorinated compounds used in pharmaceuticals, agrochemicals, and materials. We developed a photoenzymatic hydrofluoroalkylation that integrates fluorinated motifs into olefins. The photoinduced promiscuity of flavin-dependent ene-reductases enables the 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 beta, gamma, or delta positions of fluorinated groups through enzymatic hydrogen atom transfer-a process that is notably challenging with conventional chemocatalysis. This work advances enzymatic strategies for integrating fluorinated chemical feedstocks and opens avenues for asymmetric synthesis of fluorinated compounds.