Novel Proline Derivatives Synthesis And Catalytic Properties Of The Aldol Reaction

Asymmetric synthesis has a great significance for chemistry, biology, medicine and pharmacy, no matter in theory or practice. The urgent needs of single chiral spices, pesticides, pharmaceuticals, food additives, chiral liquid crystal materials and functional polymer materials, which have made the asymmetric synthesis become a hot topic in the field of chemical research.Organic molecule catalytic enantioselective reaction is based on the simulation of enzyme catalytic reaction which is a nonmetallic reaction. The organic catalytic reaction has arrived to a climax since2000, thanks to the research of List and MacMillan. Except as a strong supplement to metal-catalyzed reactions, it is non-toxic, stable in the air, the reaction can carry out in a non-absolute anhydrous solvent as well as easy operation. All the advantages of the organic catalyst attract the attention of scholars.L-proline is an effective chiral catalyst which can catalyze many organic reactions, such as Mannich,Baylis-Hillman,Michael,Diels-Alder,Aldol etc. Proline exists in the form of intramolecular salt, leading to its poor solubility in organic solvents which affects its catalytic activity and catalyst loading, thus limiting the application scope of proline. The chemical workers modificated the structure of proline and have achieved satisfactory results. However, the majority of them focus on the transformation of carboxy, less modification in the other part. The key point of our work is the synthesis of novel4-modified proline derivatives and apply them in the direct asymmetric aldol reactions, expecting good results.Based on what mentioned above, the present work is composed of the following parts:1.(2S,4R)-N-Boc-hydroxy-proline methyl ester as the raw material, after three step reactions, we synthesised the non-natural (2S,4S)-N-Boc-amino proline methyl ester;(2S,4S)-N-Boc-amino proline methyl ester as one of the reactants reacted with D-camphor sulfonyl chloride and p-toluenesulfonyl chloride respectively, obtained two prolinol sulfonamides.2.(2S,4S)-N-Boc-amino proline methyl ester as one of the reactants reacted with cinnamon chloride, crotonic chloride, salicylic chloride, terephthaloyl chloride, N-Boc-trans-4-hydroxyproline respectively, prepared five new proline derivatives. 3.(2S,4S)-4-D-camphor sulfonyl amino-proline methyl ester,(2S,4S)-4-p-toluen-esulfonyl amino-proline methyl ester and (2S,4S)-4-cinnamic acid amides proline methyl ester as catalysts catalyze the direct asymmetric aldol reaction of aromatic aldehydes and acetone. According to the results of asymmetric aldol reaction, we proposed the possible transition states.The work for testing catalytic properties of other catalysts and for adjusting the structures of these catalysts according to the test results, is still in progress.