Stereospecific Asymmetric N-Heterocyclic Carbene (NHC)-Catalyzed Redox Synthesis of Trifluoromethyl Dihydropyranones and Mechanistic Insights

Abstract

N-heterocyclic carbene (NHC)-catalyzed redox asymmetric hetero-Diels-Alder reactions of α-aroyloxyaldehydes with β-trifluoromethyl enones generates synthetically useful dihydropyranones containing a stereogenic trifluoromethyl substituent in good yields (up to 81%) and excellent diastereoselectivity and enantioselectivity (up to >95:5 dr and >99% ee). The process is stereospecific, with use of either (E)- or (Z)-β-trifluoromethyl enones forming syn- or anti-dihydropyranone products, respectively. Mechanistic studies through in situ kinetic analysis of the reaction reveal key differences in reactivity between chiral NHC precursor 1 and an achiral NHC precursor.