Organocatalytic Asymmetric Conjugate Addition Of3-Aryloxindoles To Vinyl Bisphosphonate Ester And Preliminary Investigation On The Addition Reaction Of Isocyanoacetate To Trifluoromethyl-Substituted Enones

This thesis mainly focused on the Michael addition reaction of3-aryl oxindoles to vinyl bisphosphonate ester catalyzed by a cinchona alkaloid derived thiourea catalyst and cinchona alkaloids-based squaramide catalyzed the Michael addition of α-aryl isocyanoacetates to trifluoromethyl-substituted enones.We haved developed the first example of an asymmetric Michael addition of N-Boc-3-aryloxindole to tetraethyl vinyl bisphosphonate catalyzed by a cinchonidine derived thiourea catalyst. High yields (up to92%) and good enantioselectivities (80-92%ee’s) were obtained under optimal conditions for a wide range of N-Boc-3-aryloxindole. Furthermore, the bisphosphonate adducts can be easily hydrolyzed to the corresponding acids, which provided a facile protocol to a class of new optically active gem-BP derivatives containing a tetra-substituted oxindole fragment.In addition, we also investigated the asymmetric Michael addition of α-aryl isocyanoacetates to trifluoromethyl-substituted enones catalyzed by cinchona alkaloids-based squaramide catalyst, affording the corresponding adducts in high yields (up to80%), excellent diastereoselectivitie (up to99:1dr) and excellent enantioselectivities (up to97%ee). The synthetic utility of adduct was further illustrated by transformation to potentially bioactive trifluoromethyl-substituted dihydropyrrole compound in high yield and high diastereo-selectivity by acidic hydrolysis. Investigations aimed at fully understanding the reaction mechanism and expanding the scope of trifluoromethyl-substituted enones are currently ongoing.