Synthesis Of Novel 4 - Substituted Proline Derivatives And Their Catalytic Activity For Aldol Reaction

As the third type of chiral catalysts following organometallic catalysts and enzyme, organocatalyst plays an important role in the field of asymmetric synthesis recently years. Compared with traditional organometallic catalysts and enzyme catalysts, the organocatalyst attracts more extensive attention from chemists with the unique advantages including the wealth sources, low toxicity, high efficiency, simple operation and being suitable for a wide range of substrates.With the amino and carboxyl, proline can catalyze a variety of asymmetric synthesis which effect is similar to that of enzyme. But it is necessary to make some chemical structural transformation for the proline to overcome its shortcomings, such as the poor solubility, large consumption and bad recoverability. Then proline peptides are applied to the asymmetric synthesis as catalysts and it plays an increasingly important role in this field with its special structure. In this thesis, some4-substituted proline derivatives were designed and synthesised, then they were used in the condensation reaction with4-amino-proline to prepare their dipeptide derivatives. At the same time, these dipeptide derivatives were used in the directly asymmetric Aldol reaction between aldehydes and ketones as catalysts, and their catalytic activity was investigated.The main work of this thesis composes of the following parts:First,(2S,4R)-N-Boc-4-hydroxyproline methyl ester was used as the starting material to prepare (2S,4S)-N-Boc-4-amino-proline methyl ester after the three-step preparation including esterification, nucleophilic substitution and reduction.Second, the (2S,4R)-N-Boc-4-hydroxy-proline was used to react with benzyl bromide and4-benzyl bromide to synthesize two4-benzyloxy substituted proline derivatives by Williamson. A pair of diastereoisomer (4R)-benzyloxy-proline with the partial racemization of the chiral carbon atom C-2were obtained when the (2S,4R)-N-Boc-4-hydroxyproline methyl was used as starting material. Three kinds of4-substituted amido methyl esters of L-proline derivatives were prepared from the p-toluenesulfonyl chloride, crotonic acid, cinnamic acid and (2S,4S)-N-Boc-4-amino-proline methyl ester, then the corresponding4-substituted N-Boc-protected proline derivatives were obtained by ester hydrolysis.Third, the previous five4-substituted N-Boc-protected proline derivatives and N-Boc-D-proline were used to react with4-amino-proline methyl ester respectively to synthesize five novel dipeptide N-Boc protected proline derivatives. Then the corresponding dipeptide proline methyl ester catalysts were obtained from deprotection.Fourth, the prepared diastereomers (4R)-benzyloxy-proline and three dipeptide proline methyl ester were used in the directly asymmetric Aldol reaction between4-nitrobenzaldehyde and acetone as catalysts. At the same time, the catalytic activity of these dipeptide derivatives was investigated.