Design And Application Of Chiral Organocatalysts In Catalytic Asymmetric Reactions

In recent years chemists have witnessed a spectacular advancement in asymmetric catalytic reactions based on metal-free organic molecules. In many cases, these small compounds give rise to extremely high enantioselectivities. Organocatalytic reactions are becoming powerful tools in the construction of complex molecular skeletons.The Aldol reaction ranks among the most important carbon-carbon bond-forming reactions in organic synthesis. Direct catalytic asymmetric Aldol reactions have attracted much attention, since it is highly atom efficient and easy operation. We designed a series of axially chiral L-prolinamide derivatives for a direct asymmetric aldol reaction. Some of them performed as high diastereo- and enantioselective catalysts for direct Aldol reaction of aromatic aldehydes with cycloketones, which afford Aldol products with 84%– 99% ee.Saccharines are abundant and commercially available chiral organic molecular. Here, we designed and synthesized a new class of saccharide-substituted thiourea-tertiary amine bifunctional catalysts, and their catalytic activities were evaluated in the direct Michael addition reactions of malonates to nitroolefins. Both electron-rich and electron-deficient nitrostyrenes were excellent Michael acceptors for methyl malonate. The reactions worked extremely well to afford Michael adducts in nearly quantitative yields and excellent enantioselectivities (91– 97% ee). The scope of this reaction was also extended. Whenβ-ketoester was employed, excellent yield with good diastereo- (10:90) and enantioselectivity (89.3% ee) at theβ-position of nitroolefins were obtained. These catalysts also resulted in high yields (up to 92%) and excellent enantioselectivities (up to 98% ee without recrystallization) for Mannich reaction between imines and nitromethane.Malonic acid half oxyesters (MAHOs) are shown to undergo decarboxylative ketone Aldol reactions in the presence of catalytic quantities of triethylamine. Herein we found that the modified cinchona alkaloids can catalyze the decarboxylative-Aldol reaction of malonic acid half oxyesters with trifluoromethyl ketones under metal-free conditions. When (DHQD)2AQN is used as the catalyst, it affords Aldol products in good yield with low to moderated enantioselectivity (18– 68% ee).