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Development of Highly Stereoselective Asymmetric Reactions Using P-Chiral Phosphine Ligands

使用对手性膦配体开发高度立体选择性不对称反应

基本信息

批准号：
18350017
负责人：
IMAMOTO Tsuneo
金额：
$ 10.55万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

This study is directed toward the development of new asymmetric catalysts that exhibit exceedingly high enantioselectivity and catalytic activity. In order to achieve this purpose, we designed and prepared new P-chiral phosphine ligands based on the phosphine-borane methodology. The newly synthesized phosphine ligands (QuinoxP^* and AlkynylP^*) have been proved very high enantioselectivities up to 99.9% ee in not only rhodium-catalyzed asymmetric hydrogenation but also rhodium- or palladium-catalyzed carbon-carbon bond forming reactions.A new synthetic method for the synthesis of the counter enantiomers of P-chiral phosphine ligands has been studied. A key intermediate (S)-t-butylmethylphosphine-borane, which is prepared by the use of (-)-sparteine, was converted to (R)-enantiomer by the bromination and reduction with lithium aluminum hydride. The synthesized (R)-enantiomer was used for the preparation of (R,R) t-Bu- QuinoxP^*.Mechanistic study was carried out in order to investigate the enantioselection mechanism in the rhodium-catalyzed asymmetric hydrogenation of dehydroaminoacids using (Z)-α-acetamidocinnamate as a model substrate and R-(tert-butylmethylphosphino)(di-tert-butylphosphino)methane as the chiral ligand. Based on the experimental facts and DFT caluculation, it is concluded that the enantioselection takes place during the association step when the chelating dihydride is formed from the nonchelating dihydride.

本研究旨在开发具有极高对映选择性和催化活性的新型不对称催化剂。为了实现这一目的，我们基于膦硼烷方法学，设计并制备了新的P-手性膦配体。新合成的膦配体（QuinoxP^* 和AlkynylP^*）在铑催化的不对称氢化反应和铑、钯催化的碳碳键形成反应中均表现出很高的对映选择性，最高可达99.9%ee。以（-）-鹰爪豆碱为原料，合成了一个关键中间体（S）-叔丁基甲基膦硼烷，经溴化和氢化铝锂还原，得到了（R）-对映体。以（Z）-α-乙酰氨基肉桂酸酯为模型底物，R-（叔丁基甲基膦基）（二叔丁基膦基）甲烷为手性配体，对铑催化脱氢氨基酸不对称氢化反应中的对映选择机理进行了研究.根据实验事实和密度泛函理论计算，我们认为非螯合二氢化物生成螯合二氢化物的缔合过程中发生了对映体选择性。