Development of Catalytic Enantioselective Reactions Based on the Activation Technology by Chiral Ligands

基于手性配体活化技术的催化对映选择性反应研究进展

基本信息

批准号：
10470468
负责人：
TOMIOKA Kiyoshi
金额：
$ 8.19万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

项目摘要

We have developed three types of new activation technology ; the activation of lithium ester enolates by a chiral lithium amide having ether moiety (1), of less reactive organometallic reagents, such as organozinc and organoboran by a complex of a chiral amidophosphine and a transition metal (2), and of lithium thiolate by a chiral amino ether (3).1. In the presence of a chiral lithium amide having ether moiety, thereaction of lithium ester enolates with imines gave β-lactains in up to 96% yield and 74% ee. This technology was also applicable to the addition of lithium ester enolates to α,β-unsaturated esters to give the adducts in up to 67% yield and 92% ee.2. In the presence of a catalytic amount of a chiral amidophosphine and copper(II) triflate ; the reaction of 4,4-dimethyl-2-cyclohexenone and diethylzinc gave the ethyl adduct with 64% ee. The application of this amidophosphine-copper-diethylzinc system to the reaction with imine was successful, giving ethyl adducts in up to 97% y … More ield and 94% ee. Furthermore, the chiral amidophosphine ligand was applicable to the rhodium-arylboronic acid system. In the presence of a catalytic amount of the chiral amidophosphine and rhodium(I), aryl boronic acidsreacted with 2-alkenones to provide 3-arylalkanones in up to 99% yield and 96% ee. We are accumulating the experimental evidence that the chiral amidophosphine ligand is a so-called hemilabile ligand in this rhodium complex.3. In the presence of a chiral amino ether, lithium thiolates added to α,β-unsaturated esters and the resulting lithium ester enolate was enantioselectively protonated. Thus, using α,β-unsaturated esters having no β-substitoent, the addncts with up to 92% ee were obtained. When a chiral α,β-unsaturated ester having formyl group was used as an acceptor, the intermediate lithium enolate reacted withthe formyl group in the intramolecular fashion to give cyclized products in good diastereoselectivity. This cyclization was nicely applied to the synthesis of (-)-neplanocin A. Less

我们已经开发了三种新型的激活技术。锂酯的激活通过具有醚部分的手性锂酰胺（1），具有较低的有机性有机试剂（例如有氧和有机物），通过手性氨基膦和过渡金属的复合物（2），以及甲状腺素的硫氨酸甲酸乙二醇酯通过手性氨基氨基醚（3）.1 .1 .1 .1 .1。在具有乙醚部分的手性锂酰胺的存在下，锂酯与亚胺的耐烯醇可在高达96％的产率和74％的EE中可产生β-乳酸。该技术还适用于将锂酯烯醇添加到α，β-不饱和酯中，以使加合物的产量高达67％和92％EE.2。在存在催化量的手性氨基磷蛋白和铜（II）三叶酸的情况下； 4,4-二甲基-2-环己酮和二乙基辛的反应给出了64％EE的乙基加合物。这种氨基磷酸磷酸 - 二乙基系统在与亚胺反应中的应用是成功的，可为多达97％的Y…更多和94％的EE提供乙基加合物。此外，手性氨基膦配体适用于铑 - 芳基硼酸系统。在存在催化量的手性氨基磷蛋白和若um阳化（I）的情况下，芳基硼酸与2-烷烃反应，以高达99％的产率和96％的EE提供3-芳基烷酮。累积了手性氨基膦配体是该菱形复合物中所谓的半脂配体的实验证据。3。在存在手性氨基醚的情况下，将硫酸锂添加到α，β-不饱和酯中，所得的锂酯烯烃被映射质子化。使用α-β-饱和酯，没有β-含量，获得了高达92％EE的ADDCT。当手性α，具有甲基基团的β-不饱和酯用作受体时，中间锂烯烃以分子内的方式与甲基反应，以良好的映射性提供环化产物。这种环化很好地应用于（ - ） - 元素蛋白A的合成。