Synthesis Of Cinchona Alkaloids Heterogeneous Catalysts And Applicationsin Asymmetric Reactions

Asymmetric catalysis has grown rapidly and become one of the most active and attractive research fields in asymmetric synthesis. Asymmetric catalysis as a new and powerful methodology which has three major advantages, chiral value-added, high stereoselectivity and green economy. Among them, organocatalysis has proven to be a powerful procedure for the enantioselective transformations owing to their controlled structure, low-cost raw materials, mild reaction conditions and excellent catalytic activity. However, these organocatalysts have disadvantages including the large amount of catalyst, difficult to separate from the products in homogeneous catalysis system, etc. Therefore, it is very important to develop heterogeneous catalytic systems of organocatalysts. Cinchona alkaloids derivatives are an important class of organocatalysts and show unique catalytic properties in asymmetric catalysis. In order to achieve the recycling of these catalysts, we synthesized a series of heterogeneous catalysts from cinchona alkaloids and investigated their performance in asymmetric reactions. The main contents as following:1) We prepared a series of cinchona alkaloids based imidazole ionic liquids (IL-1-IL-4). The imidazole ionic liquids have good solubility in water and we hoped that the catalysts could be reused after reaction by phase separation. We investigated applications of ionic liquids catalysts in a-chlorination of β-carbonyl carboxylates.2) We introduced active polymerizable group (styryl group) into quinidine molecular. We took divinylbenzene as crosslinking agent to synthesize a series of heterogeneous catalysts 22(a-e) by free radical polymerization. Among all catalysts, 22c showed the best catalytic activity in asymmetric a-chlorination of P-carbonyl carboxylate. We investigated applications of catalyst 22c in asymmetric a-chlorination of β-carbonyl carboxylates and obtained both moderate to good yields (75-86%) and enantioselectivity (64～86% ee). The catalyst 22c could be recycled at least four times.3) We synthesize a series of phase transfer catalysts 34(a-c) from cinchonidine by esterification, quaternary ammonium and polymerization reactions. Catalyst 34b was applied to asymmetric a-alkylation of N-(diphenylmethylene) glycine t-butyl ester, and high yields with moderate to good enantioselectivity (55-83% ee) were obtained. The catalyst 34b could be reused at least four times.