Jana, SripatiWodrich, Matthew D.Cramer, Nicolai2025-04-292025-04-292025-04-282025-12-0110.1038/s41467-025-58423-z2-s2.0-105002974809https://infoscience.epfl.ch/handle/20.500.14299/24947140195321Enantioenriched α-chiral β-fluorinated ketones are valuable structural motifs with application in several fields. The recently emerged concept of NHC-catalyzed radical acyl-trifluoromethylation of olefins offers a rapid route to construct racemic β-fluorinated ketones in a single step. Due to the lack of competent chiral NHC catalysts constructing these molecules in an enantioselective manner remains an unmet challenge. Herein, we report a family of chiral thiazolium carbenes having bulky chiral flanking groups and offering three distinct positions with broad steric and electronic tunability. The catalysts display so far unmatched enantioselectivities for acyl-trifluoromethylations of simple unactivated olefins with a wide variety of aldehydes and Togni’s reagent. The method provides a variety of enantioenriched β-trifluoromethylated α-chiral ketones in high yields and excellent enantioselectivities up to 98:2 er. A potential applicability of this methodology is demonstrated through enantio- and diastereoselective late-stage functionalizations of pharmaceutical compounds.entruetext::journal::journal article::research article