苯酞类化合物是有机化学中一类非常重要的化合物，也是天然产物家族重要的成员之一，特别值得注意的是许多光学活性3-烷基或3-芳基苯酞化合物具有良好的生物活性和药物活性，为此，高立体选择性合成这些手性苯酞化合物一直是不对称合成领域中十分引人注目的课题之一。本论文设计了以L-脯氨酸衍生物为手性诱导试剂，通过格氏试剂或锌试剂与醛的不对称加成反应获得光学活性3-烷基或3-芳基苯酞化合物的新路线，具体工作总结如下：（1） 以L-脯氨酸为原料，经保护，酯化，还原，磺酸酯化，取代及脱保护等六步反应，制备出手性助剂 (S)-1-(pyrrolidin-2-ylmethyl)-1H-imidazole。实验证明，本论文中L-脯氨酸衍生物的制备与文献方法相比，更加适于较大规模的制备及产物的纯化。（2） 将上述手性助剂通过酰胺化反应引入邻碘苯甲酸，所得的手性酰胺通过与i-PrMgCl交换反应生成手性格氏试剂，原位与醛进行加成反应，最终经酸催化下的环化反应获得光学活性苯酞化合物。通过对反应温度，反应溶剂等因素的优化，最终合成了一系列光学活性苯酞化合物，其中ee%值最高达88%。实验发现，与芳香醛加成得到的光学活性苯酞化合物ee值均在80% 以上，而与脂肪醛的加成得到的光学活性苯酞化合物ee值最高达80%。（3） 通过手性格氏试剂与ZnBr2的交换反应，本文还探索了锌试剂与芳香醛的不对称加成反应，最终所获得的光学活性苯酞化合物的ee值为71~86%。尽管锌试剂的立体选择性与格氏试剂相比，并未得到提高，但反应是在室温下进行的，操作更加方便。（4） 本文共得到10个光学活性的苯酞类化合物，所有化合物的光学活性均经液相色谱法测定，已见报道化合物的构型由旋光方向核实，结构经红外、核磁所表征。关键词：手性苯酞化合物，格氏试剂，锌试剂，立体选择性，催化关环

Phthalide is a kind of important compounds in organic chemistry, it is also an important member of the natural products family, in particular, a number of chiral 3 - alkyl or 3 - aryl- phthalides have good biological activity and pharmacentical potentials. As a result, efficient synthesis of these chiral phthalide with high stereoselectivity is one of the hot topics in the asymmetric synthesis field.In this paper, L-proline derivatives were designed as chiral inducing auxiliary, Grignard reagent or zinc reagent added to aldehydes, a new route was used to obtain optically active 3-alkyl or 3-aryl-phthalides. It can be was summarized as follows:1) Chiral auxiliary (S)-1-(pyrrolidin-2 - ylmethyl)-1H-imidazole was prepared from L-proline through protection, esterification, reduction, esterification, and deprotection. Compared with literature method, our preparation was more suitable for large-scale preparation and purification .2) Chiral auxiliary was introduced to 2-iodobenzoic acid through amidating. Exchanging of chiral amide with i-PrMgCl gave the chiral Grignard reagent. The addition reaction of chiral Grignard reagent with aldehyde was performed in situ, the optically active phthalides were finally obtained by acid-catalyzed cyclization of the addition-resulting intermediates. We optimized the reaction conditions such as temperature, solvent and other factors, and a series of optically active phthalides have been synthesized, the best enatioselectivity is up to 88%. The enatioselectivity for 3-aryl-phthalides was above 80%, on the other hand the enatioselectivity for 3 - alkyl phthalide was below 80%.3) The paper also explored the asymmetric addition reaction of the zinc reagent which was generated in suit via the transmetallation of Grignard reagent by ZnBr2 with aldehyde, the optically active phthalides were synthesized with 71 ~ 86% ee. Compared with Grignard reagent, the stereoselective of using zinc reagent were not improve, however, the reaction occurred at room temperature, the operation was more convenient.4) In this paper, a total of 10 optically active phthalides were synthesized and characterized by HLPC, IR, NMR.KEY WORDS chiral phthalide, Grignard reagent, zinc reagent, stereoselectivity, catalytic cyclization.