Work

Enantioselective acyl-trifluoromethylation of olefins by bulky thiazolium carbene catalysis

Year: 2025

Type: article

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.

Source: Nature Communications

DOI: 10.1038/s41467-025-58423-z

Authors: Sripati Jana, Matthew D. Wodrich, Nicolai Cramer

Institution: École Polytechnique Fédérale de Lausanne

Language: English

Topic: N-Heterocyclic Carbenes in Organic and Inorganic Chemistry

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: National Science Foundation, École Polytechnique Fédérale de Lausanne, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, NCCR Catalysis