Synthesis Of 4-substituted Chiral Organocatalysts Derived From L-prolines And The Catalytic Effects On The Asymmetric Direct Aldol Reaction

In the latest decade, asymmetric organocatalysis has become an important area of research in organic synthesis. Organocatalysts which are metal-free small organic molecules are able to function as efficient and selective catalysts making many organocatalytic reactions superior to those carried out using more conventional methods, and among these reactions, the aldol reaction which is recognized as one of the most powerful carbon-carbon bond-forming reactions in modern organic synthesis, creating the (3-hydroxy carbonyl structural unit found in many natural products and drugs, has received much attention in recent years.However, unlike enzymatic reactions in nature that occur in water, enantioselective organocatalytic processes have typically been carried out in organic solvents, such as DMSO, DMF, or in mixed aqueous organic solvent, under mild conditions. Therefore, highly efficient catalytic system, which gives high enantioselectivity for a broad range of substrates in water, is still limited and currently a sought-after goal in modern chemistry.In this dissertation, a new system of 4-tert-butyldimethylsiloxy substituted organocatalysts derived from N-prolylsulfonamide has been designed by our group and proved to be effective in catalyzing the direct aldol reactions of cyclic ketones with a series of aromatic aldehydes. The research showed that the best catalytic efficiency was observed with 1b. When 3 mol% of 1b was used to catalyze the reaction without using any additives in a large amount of water under mild conditions(at room temperature), the aldol products were obtained in very good yields (>99%) with excellent diastereoselectivities up to>99:1 and enantioselectivities up to>99%.