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

有机催化具有环境友好、反应条件温和等优点，一直是当前合成研究的热点。我们开发了一种手性4-吡咯烷基吡啶(PPY)类似物，它在催化活性吡啶氮附近不含手性元素。然而，该催化剂对含对二甲氨基苯甲酰基的外消旋氨基醇具有较高的对映体选择性(S=10~54)。在本研究项目中，阐明了对映体选择性酰化和对映体选择性加速的机理。结果表明，该催化剂催化氨基醇衍生物的酰化反应速度是PPY的12倍。还合成了C2对称的手性PPY类似物。以L-谷氨酸为起始原料，经五步反应得到关键中间体2，5-二羧基-N-吡咯烷。很容易实现C(2)和C(5)上官能团侧链的组合引入，从而完成了手性C2对称PPY小库的构建。所有这些新的PPY类似物对醇的酰化反应都表现出很高的催化活性，因为在具有催化活性的吡啶氮附近没有空间拥堵。在室温下，它们对环状介孔二醇的酰化不对称脱对称反应表现出很好的选择性。

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.