Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization

Опубликована: Авг. 19, 2024

The trifluoromethyl (–CF3) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made development of synthetic methods for trifluoromethylation. In contrast, there are currently no metalloenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxymandelate synthase from Amycolatopsis orientalis (AoHMS), is capable generating CF3 radicals hypervalent iodine(III) reagents and directing them enantioselective alkene azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling rapid evaluation AoHMS variants abiological transformation. final opti-mized variant accepts range substrates, producing azidation products up 73% yield 96:4 enanti-omeric ratio (e.r.). biocatalytic can be further extended pentafluoroethyl diazidation by altering reagent. addition, anion competition experiments provide insights into radical rebound process This study not only expands catalytic repertoire transformations but also creates new enzymatic space organofluorine synthesis.

Язык: Английский

Photobiocatalytic Platform for the Efficient Enantio-Divergent Synthesis of β-Fluoromethylated Ketones

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(45), С. 31012 - 31020

Опубликована: Окт. 30, 2024

β-Fluoromethyl (CH

Язык: Английский