Photoenzymatic asymmetric incorporation of fluorinated motifs into olefins

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.

能够同化氟化原料的酶类十分稀缺，这为医药、农用化学品及材料领域所用氟化化合物的生物合成带来了挑战。我们开发了一种光酶催化氢氟烷基化策略，可将氟化基序高效引入烯烃分子中。黄素依赖型烯还原酶的光诱导底物混杂性，可从碘代氟代烷烃中生成碳中心自由基，随后由光酶引导该自由基与烯烃发生对映选择性加成反应。该策略通过单个氟化单元与酶之间的相互作用实现立体调控，借助酶促氢原子转移过程，可在氟化基团的β、γ或δ位实现高对映选择性，而这一过程用传统化学催化往往难以达成。本研究推动了氟化化工原料整合相关酶促策略的发展，也为氟化化合物的不对称合成开辟了新路径。