Development of a New Generation of Nucleophilic Catalysts and their Use in Selective Reactions

有机催化因其环境友好、反应条件温和而成为当前合成领域关注的焦点。我们开发了一种手性4-吡咯烷二吡啶（PPY）类似物，该类似物在催化活性吡啶氮附近没有手性元素。该催化剂对具有对二甲氨基苯甲酰保护基团的外消旋氨基醇具有较高的对映选择性（s=10 ~ 54）。本课题主要研究了对映选择性酰基化和对映选择性加速的机理。用该催化剂催化氨基醇衍生物的酰化反应速度是用PPY催化的12倍。研究了c_2对称手性PPY类似物。通过从l-谷氨酸开始的五步序列，得到了一个关键中间体2,5-二羧基- n -吡啶吡咯烷。C(2)和C(5)官能团侧链的组合引入很容易实现，从而完成了一个小的手性c_2对称PPYs库的构建。所有这些新的PPY类似物都表现出较高的醇酰化催化活性，因为在具有催化活性的吡啶氮附近没有空间堵塞。在室温条件下，它们对环中二元醇的酰化不对称脱对称反应具有良好的选择性。

Organocatalysis has been the focus of curent synthetic attention due to environmental benignity and the mild reaction conditions. We have developed a chiral 4-pyrrolidinopyridine (PPY) analogue which has no chiral elements near the catalytically active pyridine nitrogen. Nevertheless, this catalyst shows high enantioselectivity (s=10〜54) in the kinetic resolution of racemic amino alcohols with a p-dimethylaminobenzoyl protective group. In this research project, the mechanism for the enantioselective acylation and enantioselective acceleration was clarified. The rate of acylation of an amino alcohol derivative with the catalyst was found 12 times as fast as that with PPY. C_2-symmetric chiral PPY analogues were also developed. A key intermediate, 2,5-dicarboxyl-N-pyridyl-pyrrolidine, was obtained via a five-step sequence starting from L-glutamic acid. Combinatorial introduction of the functional side chains at C(2) and C(5) is readily achieved, thus, construction of a small library of chiral C_2-symmetric PPYs was accomplished. All of these new PPY analogues showed high catalytic activity for acylation of alcohols, because of no steric congestion near the catalytically active pyridine nitrogen. They showed excellent selectivity in acylative asymmetric desymmetrization of cyclic meso-diols at room temperature.