Design And Application Of New Chiral Phase-Transfer Catalysts And Asymmetric Aldol Reaction Of Trifluoromethyl Aryl Ketones

In recent years, chiral phase-transfer catalysis (PTC) has been recognized as an important part in asymmetric synthesis due to its high activity in a series of asymmetric transformations. Herein we focused on the design and synthesis of new chiral phase-transfer catalysts and their applications in asymmetric reactions. These catalysts, bearing linker-structured N-spiroammonium units, were synthesized conveniently from commercially available optically pure 1,1'-bi-2-naphthol (BINOL) in moderate yields.The activity and enantioselectivity of the phase-transfer catalysts was firstly evaluated in catalytic asymmetric Darzens reaction between aldehydes andα-haloamides. The desiredα,β-epoxy-amides were obtained in high yields (up to 99%) with moderate to good diastereo- and enantioselectivities (trans/cis up to 13.4/1, up to 74% ee (trans)).As the analogues of the correspondingα-amino acids,α-aminophosphonic acids have diverse biological properties. However, there are rare successful examples of constructingα-aminophosphonic acids and their derivatives via C–C bond forming reactions. We first developed the Michael addition of the phosphoglycine ester toα,β-unsaturated ketones by the newly designed PTC, giving moderate to good enantioselectivities with up to 77% ee.As we all know, it is a significant strategy to apply prochiral trifluoromethyl-containing building blocks in asymmetric transformations. We accomplished the aldol-type reaction of trifluoromethyl aryl ketones withα-diazoesters, with low to moderate enantioselectivities (up to 72% ee).