Practical Synthesis of Chiral Building Blocks by Highly Efficient Catalytic Asymmetric Acylation

通过高效催化不对称酰化实际合成手性结构单元

基本信息

批准号：
12554021
负责人：
ORIYAMA Takeshi
金额：
$ 6.14万
依托单位：
IBARAKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Recently, much attention has been focused on the non-enzymatic asymmetric acylation of racemic alcohols and meso-diols. We have already demonstrated asymmetric acylation of racemic secondary alcohols and meso-l,2-diols by the reaction with achiral benzoyl halide in the presence of a catalytic amount of chiral 1 , 2-diamine derived from (S)-proline. Some papers, which are based on the catalytic asymmetric acylation of alcohols with achiral acylating agents , have emerged successively in recent years. However, neither methodology has been developed to such a level as to find widespread use in organic synthesis.We established that a chiral 1,2-diamine derived from (S)-proline could function as a highly efficient catalyst for the catalytic asymmetrization of meso- l , 2-diols. Catalytic asymmetric acylation of cw-2-cyclopentene- l ,4-diol has been successfully performed by the reaction with benzoyl chloride in the presence of 0. 5 mol% of chiral diamine combined with a stoichiometric amount of triethylamine to give the corresponding monobenzoate with excellent enantioselectivity. Thus obtained 4-benzoyloxy-2-cyclopenten-l-ol was readily converted to (R)-4-benzoyloxy-2-cyclopenten-1-one, a chiral building block for various prostaglandins, by the treatment of pyridinium dichromate (PDC). Catalytic asymmetric acylation of meso-1, 3-diols has been also successfully performed in the presence of only 0.5 mol% of chiral 1,2-diamine, combined with 1.5 equivalents of triethylamine. Catalytic kinetic resolution of racemic primary alcohols has been also performed with substituted benzoyl chloride in the presence of only 0.3 mol% of chiral 1,2-diamine derived from (S)-proline. This highly efficient asymmetric acylation of alcohols afforded various useful chiral building blocks.

最近，外消旋醇和内消旋二醇的非酶促不对称酰化受到了广泛关注。我们已经通过在催化量的衍生自(S)-脯氨酸的手性1,2-二胺存在下与非手性苯甲酰卤反应来证明外消旋仲醇和内消旋-1,2-二醇的不对称酰化。近年来陆续出现了一些基于醇与非手性酰化剂催化不对称酰化反应的论文。然而，这两种方法都尚未发展到在有机合成中广泛应用的水平。我们确定衍生自 (S)-脯氨酸的手性 1,2-二胺可以作为催化内消旋不对称化的高效催化剂。 -l,2-二醇。在 0. 5 mol% 手性二胺与化学计量的三乙胺存在下，顺式-2-环戊烯-1,4-二醇与苯甲酰氯反应成功进行催化不对称酰化，得到相应的单苯甲酸酯优异的对映选择性。通过重铬酸吡啶鎓 (PDC) 的处理，由此获得的 4-苯甲酰氧基-2-环戊烯-1-醇很容易转化为 (R)-4-苯甲酰氧基-2-环戊烯-1-酮，这是各种前列腺素的手性结构单元。仅在 0.5 mol% 手性 1,2-二胺与 1.5 当量三乙胺的存在下，内消旋 1, 3-二醇的催化不对称酰化也已成功进行。外消旋伯醇的催化动力学拆分也可以在仅 0.3 mol% 衍生自 (S)-脯氨酸的手性 1,2-二胺存在下用取代的苯甲酰氯进行。这种高效的醇不对称酰化提供了各种有用的手性结构单元。