The Study Of Asymmetric Anti-Mannich And Aldol Reactions Catalyzed By Novel Threonine-, Serine-, And Cysteine-surfactant Organocatalysts

Organic small molecule catalysts are a novel kind of organocatalysts, which are developed rapidly in recent years. It is widely used in the field of asymmetric organic synthesis. Because of its feature of environmentally friendly, non-metal and without any modification of the substrate in the reaction process,it received wide attention from researchers. So, design, synthesis of highly efficient, simple, cheap, recoverable organoctatalysts and their application for asymmetric large-scale organic reactions, is a hot research field of asymmetric organic synthesis.In this paper, firstly,after we carefully studied the structural characteristics of proteinogenic chiral threonine, serine and cysteine which had been reported previously, we designed and synthesized threonine-surfactant, serine-surfactant and cysteine-surfactant organocatalysts in one step for the first time by the reaction of threonine, serine and cysteine with acyl chlorides at room temperature in trifluoroacetic acid on a large-scale without protecting groups involved or chromatographic techniques.We first examined the ability of the threonine-surfactant organocatalysts 65a-g to promote the three-component direct anti-Mannich reaction between hydroxyacetone,4-methoxyaniline and 4-nitrobenzaldehyde under various conditions. Catalyst 65c was identified as the best catalyst for this three-component reaction which lead to Mannich adduct with excellent enantioselectivity and diastereoselectivity, ee value up to 99%, dr value up to 96:4.The three-component reactions of different aromatic aldehydes and aniline components with hydroxyacetone were studied under the optimized conditions (at 0℃, using 20 mol% of 65c as catalyst). The reactions of different aromatic aldehydes, which bear an electron-withdrawing group on the benzene ring, proceeded smoothly in excellent enantioselectivities and diastereoselectivities (yield up to 93%, ee value up to>99%, dr value 98:2) to furnish the anti-Mannich adducts. The three-component reactions of different aniline components, also proceeded smoothly in excellent enantioselectivities and diastereoselectivities (yield up to 95%, ee value up to 99%, dr value 96:4) to furnish the anti-Mannich adducts. Interestingly, this novel catalyst can be efficiently used in large-scale reactions, with the enantioselectivity being maintained at the same level, which offers great possibilities for application in industry.Finally, we studied direct aldol reaction of ketone and different aromatic aldehydes. In case of catalyst 65c and 65f, the reaction was carried out under the optimized conditions (at room temperature, using 5 mol% of 65c and 65f as catalyst). The reactions of different aromatic aldehydes proceeded smoothly in excellent enantioselectivities and diastereoselectivities (yield up to 99%, ee value up to>99%, dr value 99:1) to furnish the aldol adducts. Interestingly, this novel catalyst can be easily recovered and reused with no decrease of enantioselectivity, and this novel catalyst can be efficiently used in large-scale reactions, with the enantioselectivity being maintained at the same level, which offers great possibilities for application in industry.We also studied direct stoichiometric aldol reaction of different ketones and different aromatic aldehydes. In case of catalyst 65i, the stoichiometric reactions were carried out under the optimized conditions (at room temperature, using 1 mol% of 1a as catalyst). The reactions of different aromatic aldehydes proceeded smoothly in excellent enantioselectivities and diastereoselectivities (ee value up to>99%, dr value 99:1) to furnish the aldol adducts. Interestingly, this novel catalyst can be easily recovered and reused with no decrease of enantioselectivity, and this novel catalyst can be efficiently used in large-scale reactions, with the enantioselectivity being maintained at the same level, which offers great possibilities for application in industry.We first examined the ability of the serine-surfactant organocatalysts 66a-h to promote the direct aldol reaction between different ketones and different aromatic aldehydes under various conditions. Catalyst 66b was identified as the best catalyst for this reaction which lead to aldol adduct with excellent enantioselectivities and diastereoselectivities (up to 99:1), ee value up to 99%. The catalyst 66b can be easily recovered and reused and can be efficiently used in large-scale reactions. We also examined the ability of the cysteine-surfactant organocatalysts 67a-f to promote the direct stoichiometric aldol reactions between different ketones and different aromatic aldehydes under various conditions, and The catalyst 67c can be efficiently used in large-scale reactions.Via the researching work of this dissertation, we hope that we can provide preliminary theoretical basis for design of new organocatalysts based on amino acids, and provide reference for development of catalyst diversity. As the time goes on, We believe that in the near future, as the studies in organocatalysis goes deeper and wider, as the use of resourses more reseaonable, as the protection to environments and sustainable development been paid more attention to, its application will not be limited in research but also in industry.