NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides (Beilstein Journal of Organic Chemistry)

Abstract The N-heterocyclic carbene (NHC)-catalyzed formal [2 + 2] cycloaddition between α-aroyloxyaldehydes and trifluoroacetophenones, followed by ring opening with an amine or a reducing agent is described. The resulting β-trifluoromethyl-β-hydroxyamide and alcohol products are produced with reasonable diastereocontrol (typically ≈70:30 dr) and excellent enantioselectivity, and they can be isolated in moderate to good yield as a single diastereoisomer. Beilstein J. Org. Chem. 2020, 16, 1572–1578. doi:10.3762/bjoc.16.129