Synthesis Of Polymer Supported L-proline-thiourea Derivatives And Their Catalytic Properties For Asymmetric Reactions

Organocatalysis is one of the most attractive directions in the field of asymmetric synthesis where the design and synthesis of organocatalysts is the key point and hotspot. With ongoing of the research on organocatalysts such as L-proline, thiourea, and quinine, the preparation of organocatalysts possessing increased activity and selectivity is becoming more and more challenging. Recently, polymer-supported organocatalysts as a newly emerging branch in the field of organocatalysis have been attracting intensified attention in relation to design, synthesis, and catalytic performance evaluation. Polymer-supported organocatalysts not only favor recycle and reuse to offset the drawbacks of organic small-molecules but also possess improved catalytic properties owing to their spatial structure, which helps to inject new vitality into the field of organocatalysis. In this context, we have designed a series of novel bifunctional organocatalysts by rationally integrating the structural merits of organic small molecules L-proline and thiourea and synthesized six polymer-supported L-proline-thiourea derivatives by using Merrifield resin, polyvinyl chloride (PVC) and chitosan as the supports. Resultant derivatives were used to catalyze direct asymmetric Aldol reaction and asymmetric Henry reaction for the purpose of evaluating their catalytic performance. The main contents and research results of the present thesis are as follows:1. Preparation of Merrifield resin-supported L-proline-thiourea derivatives and evaluation of their catalytic performance for asymmetric Aldol reaction and Henry reactionFour Merrifield resin-supported L-proline-thiourea derivatives were synthesized via the reaction of functional Merrifield resin with isothiocyanate of proline in the presence of various polyamines as the linkers. The chemical structures of intermediates and target products were characterized by means of infrared spectrometry (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. In the meantime,The catalytic performance of resultant synthetic products for the direct asymmetric Aldol reaction between ketones and aromatic aldehydes as well as for the asymmetric Henry reaction between aromatic aldehydes and nitromethane was evaluated. It has been found that all the four kinds of resin-supported thiourea organocatalysts are efficient for Aldol reactions under research; whether water is contained as a solvent in the reaction system or not, they have excellent enantioselectivities and high activities even at a small dosage of 2 mol % which is similar to that of organic small molecules. Besides, catalysts can be recovered and reused for at least four cycles without significant loss of selectivity. Moreover, when THF and diethylamine were used as the solvent as base, respectively, as-synthesized Merrifield resin-supported L-proline-thiourea derivatives possessed a moderate stereoselectivity for the asymmetric Henry reaction between aromatic aldehydes and nitromethane, but the yield was not high.2. Preparation of polyvinyl chloride-supported L-proline-thiourea derivative and evaluation of its catalytic performance for asymmetric Aldol reactionA polyvinyl chloride-supported L-proline-thiourea derivative was developed and was charactered by means of infrared spectrometry. The target product was tested as a novel bifunctional organocatalyst for the direct asymmetric Aldol reaction. It has been found that polyvinyl chloride-supported L-proline-thiourea derivative possesses good catalytic activity and stereoselectivities at room temperature in water, while its reusability under optimal reaction conditions is good. By comparing with the same catalyst without thiourea moiety, we can infer that the introduction of thiourea moiety in L-proline endows it with significantly increased activity and selectivity, making it feasible to efficiently manipulate Aldol reaction.3. Preparation of a chitosan-supported L-proline-thiourea derivative and evaluation of its catalytic performance for asymmetric Aldol reactionA hydrophilic chitosan-supported L-proline-thiourea catalyst was prepared by using chitosan as the support. Its catalytic performance for the asymmetric Aldol reaction between ketones and aromatic aldehydes was evaluated, and its adaptability to substrates and recyclability were investigated. It has been found that, regardless of the substituent electronic nature, as-synthesized chitosan-supported L-proline-thiourea catalyst possesses high activity and stereoselectivities as well as a wider substrate scope than the above-mentioned two types of polymer-supported catalysts. In the meantime, this hydrophilic catalyst possesses good recyclability, and its enantioselectivity remains almost unchanged after it is recycled for at least four times.