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

本研究旨在基于新型手性膦配体的设计和合成，开发新的催化不对称反应。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新型四膦配体，并用单晶X-射线衍射法测定了其分子结构。四膦配体本身是C_2对称的，但每个Rh-双膦球体形成一个C_1对称的三阻象限。在Rh催化的脱氢氨基酸不对称氢化反应中，该化合物表现出良好的对映体诱导能力。通过低温加氢反应，得到了一个定量的四氢罗络合物，并研究了该络合物与烯烃底物的反应，以阐明其详细的对映体选择机理。通过假设…可以合理地解释包括立体化学结果在内的结果本文合成了一种新的对手性膦酚，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。反应在温和的条件下顺利进行，得到了相应的产物，对映体过量高达96%。用我们实验室制备的几种手性膦配体对简酮的不对称硅氢化反应进行了研究。当使用体积庞大的硅烷化试剂如α-naphtyl二苯基硅烷时，观察到非常高的对映选择性，高达99%。考虑到对映体选择发生在迁移插入步骤，使立体选择的意义合理化，设计并合成了一种新的P-手性双膦配体(R，R)-2，3-bis(tert-butylmethylphosphino)quinoxaline(QuinoxP^*))，它是由对映体纯的(R)-tert-butyl(hydroxymethyl)methylphosphine-borane与2，3-二氯喹恶啉反应合成的。与以前报道的大多数P-手性配体不同，该配体是一种空气稳定的固体，在Rh催化的不对称氢化反应和Rh或Pd催化的碳-碳键形成反应中都表现出良好的对映选择性。较少

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