Jana S,
Wodrich MD,
Cramer N *.
Ecole Polytechnique Fédérale de Lausanne, Switzerland
Enantioselective Acyl-Trifluoromethylation of Olefins by Bulky Thiazolium Carbene
Catalysis.
Nat. Commun. 2025;
16: 3293
DOI:
10.1038/s41467-025-58423-z
Keywords
α-chiral β-fluoroalkylated ketones - asymmetric radical acyl-trifluoromethylation
- thiazolium carbenes
Significance
Cramer and co-workers disclose the asymmetric acyl-trifluoromethylation of olefins
using a thiazolium carbene as catalyst. The α-chiral β-fluoroalkylated ketones are
obtained in moderate to very good yield (46–82 %) and with good to excellent enantioselectivity
(91:9 to 98:2 er). The replacement of Togni’s reagent (3) by a modified hypervalent iodine reagent enables the introduction of diverse fluoroalkyl
groups in the β-position. This facilitates access to a broad range of valuable, enantioenriched
α-chiral β-fluoroalkyl ketones.
Comment
Previous reports on N-heterocyclic carbene (NHC)-catalyzed acyl-fluoroalkylation of
olefins established racemic and asymmetric routes up to 60:40 er. Nevertheless, a
highly enantioselective reaction remained elusive. Starting from a reported, asymmetric
variant of the best-performing achiral catalyst, Cramer and co-workers show how the
optimization of electronic and steric parameters can be synergistically combined to
yield a highly enantioselective NHC-based catalyst that can convert simple, unactivated
olefins as well as pharmaceutical derivatives.
