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，人们关注的是外消旋醇和中二醇的非酶不对称酰化。我们已经证明，在催化量的手性1，源自（S） - 磷的催化量的手性1，在催化量的手性1中，与苯甲酰卤化物的反应不对称酰化。近年来，一些基于醇含醇的催化不对称酰基化的论文已持续出现。但是，这两种方法都没有开发到有机合成中广泛使用的水平。我们确定，源自（S） - 磷的手性1,2-二胺可以作为高效的催化剂，用于催化催化剂的催化剂，以催化催化剂的催化剂。在0. 5 mol％的手性丁胺的存在下，与苯甲酰氯化物的反应成功地进行了CW-2-氯苯甲酸，4-二醇的催化不对称酰基化，与苯二氨基二醇的反应结合在一起，结合了刻板量的三乙他胺，使相应的单一生成型单基因齐酸盐具有出色的单基因齐甲酸。因此，获得的4-苯甲酰氧基-2-循环l-ol很容易被转换为（R）-4-苯甲酰氧基-2-Cyclopenten-1-One，这是一种用于各种前列腺素的手性构建块，通过治疗吡啶素二核酸盐（PDC）。在仅0.5 mol％的手性1,2-二胺的存在下，在中二二胺的催化不对称酰化也已成功进行，并结合了1.5等效的三乙胺。在仅在（S） - proline衍生的手性的1,2-二胺的0.3 mol％的情况下，还用替代的苯甲酰氯化物进行催化动力学分辨率。这种高效的酒精不对称酰基化提供了各种有用的手性构件。