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

本研究旨在阐明铑催化的不对称氢化反应的对映体选择性机理。在本研究中使用了P-手性、富电子的二膦，如BisP^* 和MiniPHOS，因为它们的分子结构简单，在铑催化的α-或β-和脱氢氨基酸衍生物、酰胺和烯醇酯的不对称氢化中具有非常高的对映体诱导能力。最重要的发现之一是检测和表征铑二氢化物配合物轴承双膦配体。二氢化物在-100 ~-90 ℃下与烯烃底物反应生成相应的一氢化物中间体，随后在-50 ℃左右发生还原消除反应。这些结果被解释为考虑二氢化物机制。结果表明，对映选择性是在Rh-H迁移插入C-C双键的阶段决定的。控制对映体选择性的主要因素有：1。通过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.螯合循环的形成，4。磷上的大体积基团与螯合循环之间的空间相互作用，5。烯基上取代基的电子效应。同时还表明，这些铑催化的不对称氢化反应的对映选择性受多种立体调控因素的控制。提出了一个新的四分法则，用于关联加氢产物的立体化学与催化剂结构之间的关系。在此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.