手性仲烯丙醇的立体选择性合成研究及其应用

项目名称： 手性仲烯丙醇的立体选择性合成研究及其应用

项目编号： No.21302066

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 范为正

作者单位： 江南大学

项目金额： 25万元

中文摘要： 在过去的几十年里，合成手性仲烯丙醇的方法得到了很大的发展，如对消旋的烯丙醇进行动力学拆分、α,β-烯基酮的不对称还原以及α,β-烯基醛的不对称加成等，但发展一种高对映选择性的、高立体选择性的直接合成手性仲烯丙醇的方法仍是当今化学领域的极具挑战性的课题。本项目以方便易得的、光学纯的环氧化合物为起始原料，将其转化成羰基烯烃化试剂后与醛、酮反应来构建手性仲烯丙醇的碳碳双键并引入手性羟基，解决了传统方法引入手性羟基可能只有中等或较低的对映选择性问题，并且通过将环氧化合物转化成不同形式的羰基烯烃化试剂来实现立体选择性地合成手性仲烯丙醇。此外，本项目以环氧氯丙烷为起始原料还可以在合成手性仲烯丙醇的同时在羟基的邻位引入了卤原子，而该中间体可以为他汀类降血脂药物以及其它重要手性分子的合成提供一种便捷的方法。

中文关键词： 手性；立体选择性；仲烯丙醇；碳碳双键；他汀

英文摘要： Many methodologies for preparation of optically pure sec-allyic alcohols have been developed by organic chemists in the past decades, such as kinetic resolution of racemic sec-allylic alcohols, asymmetric reduction of α,β-unsaturated ketones, and asymmetric addition of α,β-unsaturated aldehydes. However，the directe stereoselective synthesis of chiral sec-allylic alcohols with high enantioselectivities is still a challenge work.In this program, we decide to develop a new method by using convenient and commercially available and optically pure epoxy compounds to prepare carbonyl olefination reagents and then react with ketones or aldehydes to afford the optically pure sec-allylic alocohols. This methodology can avoid moderate or low enantioselectivities of sec-allylic alcohols produced by traditional methods. Additionally, this method can provide a stereoselcetive synthesis of the E- or Z- sec-allylic alcohols. Furthermore, when we utilize the epoxy chloride as starting material，the chloride is also introduced in the vicinity of the hydoxy group during the construction of sec-allylic alcohols. Lastly, the optically pure sec-allylic alcohols with E selectivity also can be served as key intermediate in the synthesis of the statin drugs and some other important complex molecules.

英文关键词： Chirality；Stereoselectivity；sec-Allylic alcohols；C=C double bond；statin