Nielsen Robert J, Keith Jason M, Stoltz Brian M, Goddard William A
Materials and Process Simulation Center, Beckman Institute (139-74), and The Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
J Am Chem Soc. 2004 Jun 30;126(25):7967-74. doi: 10.1021/ja031911m.
The key interactions responsible for the unique reactivity of (-)-sparteine-PdX(2) complexes (X = chloride, acetate) in the enantioselective oxidation of secondary alcohols have been elucidated using quantum mechanics (B3LYP DFT with the PBF polarizable continuum solvent model). From examining many possible pathways, we find the mechanism involves: (1) substitution of the alcohol in place of an X-group, (2) deprotonation of the bound alcohol by the deposed anion and free sparteine, (3) beta-hydride elimination through a four-coordinate transition state in which the second anion is displaced but tightly associated, (4) replacement of the ketone product with the associated anion. The enantioselectivities observed under base-rich reaction conditions follow directly from calculated energies of diastereomeric beta-hydride elimination transition states incorporating (R) and (S) substrates. This relationship reveals an important role of the anion, namely to communicate the steric interaction of the ligand on one side of the Pd(II) square plane and the substrate on the other side. When no anion is included, no enantioselectivity is predicted. Locating these transition states in different solvents shows that higher dielectrics stabilize the charge separation between the anion and metal and draw the anion farther into solution. Thus, the solvent influences the barrier height (rate) and selectivity of the oxidation.
利用量子力学（采用PBF可极化连续介质溶剂模型的B3LYP密度泛函理论）阐明了（-）-鹰爪豆碱-PdX₂配合物（X = 氯、乙酸根）在仲醇对映选择性氧化反应中具有独特反应活性的关键相互作用。通过研究许多可能的反应途径，我们发现其反应机理涉及：（1）醇取代X基团；（2）被取代的阴离子和游离的鹰爪豆碱使配位的醇去质子化；（3）通过四配位过渡态进行β-氢消除，其中第二个阴离子被取代但紧密相连；（4）相关阴离子取代酮产物。在富碱反应条件下观察到的对映选择性直接源于结合（R）和（S）底物的非对映体β-氢消除过渡态的计算能量。这种关系揭示了阴离子的重要作用，即传递Pd（II）正方形平面一侧配体与另一侧底物的空间相互作用。当不包含阴离子时，预测没有对映选择性。在不同溶剂中定位这些过渡态表明，较高的介电常数稳定了阴离子与金属之间的电荷分离，并使阴离子更深入地进入溶液。因此，溶剂影响氧化反应的势垒高度（速率）和选择性。
