Design, Development And Synthesis Of Novel Organocatalysts Of Thiourea As Well As Their Application In Asymmetric Catalysis

Abstract:The catalytic asymmetric synthesis is the most popular and challenging in all of the asymmetric synthesis. Thousands of products can be prepared in catalytic asymmetric synthesis, which is similar to the enzymatic catalytic reaction in the biological system. Taking the cost into consideration, it possesses the incomparable advantage over the stoichiometric asymmetric synthesis, especially in industrial production. The catalytic asymmetric reaction is one of the most effective pathway to obtain the required stereochemical configuration materials and enhance asymmetric value. Therefore, the development of new chiral catalysts with high selectivity and catalytic reactivity has become the pivot in the asymmetric synthesis.Over the past years, organocatalysts bearing hydrogen-bonding activating groups have attracted intensive interest. The double hydrogen-bonding interaction of N-H between urea (or thiourea) and substrate has been generally found to play a important role in the catalytic reactivity and enantioselectivity. In this thesis, we designed and synthesized6types of novel chiral thiourea molecules by using the cheap L-alanine and L-phenylalanine as the starting materials, which are2,4,6-trimethylbenzene sulfonamide thiourea,2,4,6-trimethylbenzene sulfonamide thiourea,p-dodecylbenzene sulfonyl hydrazide thiourea, p-dodecylbenzene sulfonyl hydrazide thiourea, p-dodecylbenzene sulfonic acid amide thiourea, p-methylbenzenesulfonamide thiourea. The structures of these compounds were confirmed via proton nuclear magnetic resonance spectroscopy (1H-NMR), nuclear magnetic resonance spectroscopy (13C-NMR) and infrared spectroscopy (IR). They were applied in various asymmetric reactions and prepliminary results were obtained.The test results show that such dual-functional thiourea-sulfonamide catalysts are capable of catalyzing the asymmetric Michael addition reaction between indole and nitrostyrene and the kinetic resolution of secondary alcohols. Furthermore, we proposed an action model between the catalyst and substrate and the transition state through multiple hydrogen-bonding formation. The mechanism of interaction between thiourea-sulfonamide catalyst with the substrate was investigated at the molecular level, which would facilitate the studies on the structure-activity relationship and the further improvement of the catalytic reactivity and enantioselectivity for this type of catalyst.