NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

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.

Keywords

• enantioselective catalysis
• formal [2 + 2] cycloaddition
• n-heterocyclic carbene
• ring opening
• trifluoromethyl group