NHC-Mediated Radical Acylation Catalyzed by Thiamine- and Flavin-Dependent Enzymes

• DOI: 10.1021/jacs.5c04484
• Publication Date: 2025-04-15T14:51:52Z
• Authors: Shunsuke Kato; Shuto Fujisawa; Yuto Adachi; Mitsuhiro Bandai; Yutaro Mori; Seiji Mori; Tomokazu Shirai; Takashi Hayashi

Cross-coupling reactions between short-lifetime radicals are challenging in organic chemistry. Here, we report the development of an N-heterocyclic carbene (NHC)-mediated radical coupling reaction based on catalytic machinery thiamine- and flavin-dependent enzymes. Through a series enzyme screenings, found that acetolactate synthase from Thermobispora bispora (TbALS) its engineered variants exhibit promising activity toward abiotic acylation α-bromo carbonyl compounds. Notably, TbALS variant has higher for small nonaromatic substrates despite forming less stable intermediates. Furthermore, system can be applied to photocatalytic utilizing photoredox properties FAD. Nonbenzylic alkyl generated N-acyloxyphthalimides efficiently converted into corresponding dialkyl ketones under irradiation blue LED. These findings highlight utility enzymes achieving selective cross-coupling radicals.