Elucidation of the Enantioselection Mechanism of Transition Metal-Catalyzed Asymmetric Reactions

本研究旨在阐明具有代表性的不对称催化剂之一--铑催化的不对称氢化反应的对映选择性机理。在这项研究中使用了手性的富含电子的双膦配体，如BISP^*和MiniPHOS，因为它们的分子结构简单，并且在α-或β-和脱氢氨基酸衍生物、烯胺和烯醇酯的不对称催化氢化反应中具有很强的对映诱导能力。最重要的发现之一是检测和表征了含双膦配体的二氢化铑配合物。即使在-10 0~-90℃时，二氢化合物也很容易与烯烃底物反应生成相应的一氢化合物中间体，随后在-5 0℃左右发生还原消除。这些结果是通过考虑二氢化合机理来解释的。结果表明，对映体选择性是在Rh-H向C-C双键的迁移插入阶段决定的。影响对映体选择性的主要因素有：1.配位磷原子的反式作用；2.Rh-H与C-C双键之间的轨道相互作用；3.螯合环的形成；4.磷基团与螯合环之间的空间相互作用；5.烯基取代基的电子效应。结果还表明，Rh催化的不对称氢化反应的对映选择性受多种立体调控因子控制。提出了加氢产物的立体化学与催化剂结构相关联的新象限规则。在这些研究成果的基础上，设计合成了一种新型高效的手性双膦配体。

This study is directed toward the elucidation of the enantioselection mechanism of rhodium-catalyzed asymmetric hydrogenation that is one of the representative asymmetric catalyses. P-Chirogenic, electron-rich diphosphines such as BisP^* and MiniPHOS were used in this study because of their simple molecular structure and very high enantioinduction ability in rhodium-catalyzed asymmetric hydrogenations of α- or β-and dehydroamino acid derivatives, enamides, and enol esters. One of the most important findings is the detection and characterization of the rhodium dihydride complexes bearing diphosphine ligands. The dihydride complexes reacted readily with the alkene substrates even at -100 - -90 ℃ to give the corresponding monohydride intermediates, and subsequent reductive elimination occurred at about -50 ℃. These results are interpreted by considering a dihydride mechanism. It is concluded that the enantioselection is determined at the stage of the migratory insertion of the Rh-H to the C-C double bond. The main factors to control the enantioselection are 1. Trans effect of by the coordinated phosphorus atom, 2. The orbital interaction between of the Rh-H and the C-C double bond, 3. Formation of the chelate cycle, 4. The steric interaction between the bulky group at the phosphorus and the chelate cycle, 5. Electronic effect of the substituent at the olefic group. It is also concluded that the enantioselection of these Rh-catalyzed asymmetric hydrogenations is governed by multi stereo regulation factors. A new quadrant rule to correlate between the stereochemistry of the hydrogenation products and the structure of the catalyst structures has been proposed. A new, highly efficient chiral diphosphine ligand has been designed and synthesized based on these research results.