Development of New Catalytic Asymmetric Reactions Based on the Synthesis of Optically Active Phosphine Ligands

本论文的主要目的是设计和合成新型手性膦配体，并以此为基础发展新型的不对称催化反应。以膦-硼烷为中间体，合成了一种在磷原子上具有四个手性中心的四膦配体，并通过单晶X射线衍射分析确定了其铑配合物的分子结构。四膦配体本身是C_2对称的，但每个Rh-二膦球形成一个C_1对称的三位阻象限。该配合物在铑催化脱氢氨基酸的不对称氢化反应中表现出良好的对映体诱导能力。配合物的低温氢化定量得到四氢铑配合物，并研究了四氢铑配合物与烯烃底物的反应，以阐明详细的对映体选择性机制。包括立体化学结果在内的结果可以通过假设 关于我们 合成了一种新的对映体膦酚，并将其用于铜催化的α，β-不饱和羰基化合物的不对称共轭加成反应。反应条件温和，产物的对映体过量高达96%。利用本实验室合成的几种手性膦配体对简单酮的不对称硅氢化反应进行了研究。当使用大体积的硅烷化试剂如α-萘基二苯基硅烷时，观察到高达99%的非常高的对映选择性。通过对映体纯的（R）-叔丁基（羟甲基）甲基膦硼烷与2，3-二氯喹喔啉反应，设计并合成了一种新的P-手性双膦配体（R，R）-2，3-二（叔丁基甲基膦基）喹喔啉（QuinoxP^*）。该配体，在大多数以前报道的P-手性配体相比，是一个空气稳定的固体，并表现出优异的对映选择性，在铑催化的不对称氢化和铑或钯催化的碳-碳键形成反应。少

This study is directed toward the development of new catalytic asymmetric reactions based on the design and synthesis of novel chiral phosphine ligands. A new tetraphosphine ligand bearing their four chiral centers at phosphorus atoms has been synthesized via phosphine-boranes as the intermediates and the molecular structure of its dirhodium complex was determined by the single crystal X-ray analysis. The tetraphosphine lidand itself is C_2 symmetric, but each Rh-diphosphine sphere forms a C_1 symmetric three-hindered quadrant. This dirhodium complex exhibited excellent enantioinduction ability in Rh-catalyzed asymmetric hydrogenation of dehydroamino acids. Low temperature hydrogenation of the complex afforded a tetrahydrorhodium complex quantitatively, and the reactions of the tetrahydride complex with alkene substrates were studied in order to elucidate the detailed enantioselection mechanism. The results including the stereochemical outcome are reasonably interpreted by assuming tha … More t the enantioselection would be determined at the migratory insertion step.A new P-chiral phosphinophenol was prepared and employed in copper-catalyzed asymmetric conjugate addition to α,β-unsaturated carbonyl compounds. The reactions proceeded smoothly under mild conditions to afford the corresponding products with high enantiomeric excesses of up to 96%.Asymmetric hydrosilylation of simple ketones was tested by the use of several P-chiral phosphine ligands prepared in our laboratory. Very high enantioselectivity of up to 99% was observed when a bulky silylation reagent such as α-naphtyldiphenylsilane was used. The sense of the stereoselection has been rationalized by considering that the enantioselection occurs at the migratory insertion step.A new P-chiral diphosphine ligand, (R,R)-2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP^*)) was designed and synthesized by reacting enantiomerically pure (R)-tert-butyl(hydroxymethyl)methylphosphine-borane with 2,3-dichloroquinoxaline. This ligand, in contrast to most of the previously reported P-chiral ligands, is an air-stable solid and exhibits excellent enantioselectivities in both Rh-catalyzed asymmetric hydrogenations and Rh- or Pd-catalyzed carbon-carbon bond-forming reactions. Less