Enantioselective acyl-trifluoromethylation of olefins by bulky thiazolium carbene catalysis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40195321.
- Also identified by DOI 10.1038/s41467-025-58423-z and PMC identifier 11977197.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Enantioenriched 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.