Synthesis Of Chiral Catalysts Derived From L-prolines And The Catalytic Effects On The Asymmetric Direct Aldol Reaction, Michael Addition Reaction

Asymmetric organocatalysis has emerged as a rapidly growing and important field in organic chemistry. The search for small molecules that are able to act as catalysts in enantioselective transformations has received extensive attention during the last decade, and small molecules as organocatalysis brought the prospect of a complementary mode of catalysis, with the potential for savings in cost, time and energy, an easier experimental procedure, and reductions in chemical waste. Not surprisingly, proline and derivatives have become an important part of the small molecules catalytic.Aldol reaction constitutes one of the immensely investigated amongst carbon-carbon bond forming reactions in the realm of organocatalysis. These compounds are generally prolinamide derivatives that differ in the nature of the amine component attached to the carboxylic functionality of proline, and generally contain additional stereogenic center and hydrogen-bonding site. Therefore, these catalysts are not only complex but also expensive as a rule. One of the major limitations using organocatalyst catalyzed reactions is the high catalyst loading (10-30 mol%) generally required to complete the transformations in large equivalents ketone in reasonable timescales. This will raise a cost concern when large amounts of chiral materials are used for a large-scale synthesis in industrial applications.With the aim to discover a simple, cheap and efficient route to highly enantiomerically enriched anti-aldol products catalyzed by simple prolinamides and offer great possibility for applications in industry, we prepared prolinamines 1a-1e and 2a-2d. It is shown that prolinamides 1a-e and 2a-d exhibited great catalytic activity in the asymmetric aldol reaction in m-xylene at-20℃only with 5 mol% catalyst loading in 4 equivalents ketone. And afforded aldol products in a high diastereoselectivity (up to anti/syn 99:1) and enantioselectivity (99%) and significantly enhanced reaction yield (99%). The catalyst 2a can be easily recovered and reused, and without significant decrease of enantioselectivity was observed for five cycles. Furthermore, this cheap, simple and recyclable catalyst can be efficiently used in large-scale reactions with the enantioselectivities being maintained at the same level, which offers a great possibility for application in industry.Micheal reaction is also recognized as one of the most powerful carbon-carbon bond-forming reactions in modern organic synthesis, and organic small molecules catalytic asymmetrical Michael addition reaction have become a hot topic in the domestic and foreign in asymmetrical catalytic. However, this 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 develop the excellent catalytic system will be a goal of continue to pursue.In this paper, a kind of different links of diphenylperhydroindolinol silyl ethers was synthesized from proline, and they were evaluated for asymmetric Michael reaction. The results show that different links of catalyst performance of the different catalytic activity in organic solvents and the water. Catalyst 4a is the best in the organic solvents and 4c is the best in the water.