Gridnev Ilya D, Imamoto Tsuneo, Hoge Garrett, Kouchi Mitsuhiro, Takahashi Hidetoshi
Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8552, Japan.
J Am Chem Soc. 2008 Feb 27;130(8):2560-72. doi: 10.1021/ja076542z. Epub 2008 Feb 1.
The rhodium complex of (R)-(tert-butylmethylphosphino)(di-tert-butylphosphino)methane used in Rh-catalyzed asymmetric hydrogenation of representative substrates 3-14 demonstrated high catalytic activity coupled with wide scope and nearly perfect enantioselectivity. Mechanistic studies (NMR and DFT computations) were carried out in order to investigate the mechanism of the enantioselection in the asymmetric hydrogenation of (Z)-alpha-acetamidocinnamate (3). Although catalyst-substrate complexes 15a,b with the double bond coordinated near the non-"chiral" phosphorus atom were formed as kinetic products upon the addition of 3 to solvate complex 2 at -100 degrees C, they rapidly rearranged to more stable isomers 15c,d with the double bond coordinated near the "chiral" phosphorus atom. The thermodynamic and kinetic parameters of the interconversion between 15c and 15d were determined by NMR; mainly, the interconversion occurred intramolecularly via nonchelating catalyst-substrate complexes 16. The equilibrium between 15d and 16d was directly observed from NMR line shape changes at temperatures ranging from -100 to -40 degrees C, whereas no such equilibrium was observed for 15c. This result was accounted for computationally by determining the corresponding transition states for the methanol insertion into 15c,d. Three sets of experiments of the low-temperature hydrogenation of different catalyst-substrate complexes gave the same order and sense of enantioselectivity (97% ee (R)) even in the case when 15c, having Re-coordinated double bond, was hydrogenated under the conditions precluding its isomerization to 15d. It was concluded that the hydrogenation of 15c,d does not occur directly, but is preceded by the dissociation of the double bond to result in the more reactive species 16. This indicates that enantioselection must occur at a later step of the catalytic cycle. DFT computations of association and migratory insertion steps suggest that enantioselection takes place during the association step when chelating dihydride 19d.MeOH is formed from nonchelating dihydride 18d.
用于铑催化代表性底物3 - 14不对称氢化反应的(R)-(叔丁基甲基膦基)(二叔丁基膦基)甲烷铑配合物表现出高催化活性、广泛的底物适应性以及近乎完美的对映选择性。为了研究(Z)-α-乙酰氨基肉桂酸酯(3)不对称氢化反应中的对映选择性机理，进行了机理研究（核磁共振和密度泛函理论计算）。尽管在-100℃将3加入溶剂化配合物2时，形成了双键配位在非“手性”磷原子附近的催化剂-底物配合物15a,b作为动力学产物，但它们会迅速重排为更稳定的异构体15c,d，双键配位在“手性”磷原子附近。通过核磁共振确定了15c和15d之间相互转化的热力学和动力学参数；主要是，相互转化通过非螯合的催化剂-底物配合物16在分子内发生。在-100至-40℃的温度范围内，从核磁共振谱线形状变化直接观察到了15d和16d之间的平衡，而对于15c未观察到这种平衡。通过确定甲醇插入15c,d的相应过渡态，用计算方法解释了这一结果。即使在排除15c异构化为15d的条件下将具有Re-配位双键的15c氢化，三组不同催化剂-底物配合物的低温氢化实验也给出了相同顺序和方向的对映选择性（97% ee (R)）。得出的结论是，15c,d的氢化不是直接发生的，而是在双键解离导致形成更具反应活性的物种16之后发生。这表明对映选择性一定发生在催化循环的后期步骤。缔合和迁移插入步骤的密度泛函理论计算表明，当从非螯合二氢化物18d形成螯合二氢化物19d·MeOH时，对映选择性发生在缔合步骤。
