UM-DAE Centre for Excellence in Basic Sciences, Health Centre, University of Mumbai , Vidyanagari Campus, Kalina, Santacruz (East), Mumbai 400098, India.
J Org Chem. 2018 Feb 2;83(3):1304-1311. doi: 10.1021/acs.joc.7b02822. Epub 2018 Jan 23.
We describe the computational study of an interesting class of reactions involving synergistic action of chiral amine and Cu catalyst. The stereoselectivity-determining step of the enantioselective α-alkenylation of aldehyde has been investigated using the density functional theory methods to gain insight into the origin of the product selectivity. We found that the catalytic activation of reactants in the form of enamine and alkenyl Cu(III) intermediates significantly reduces the activation barrier of the addition step through an improved interaction between these two intermediates at the transition state (referred as enamine and Cu catalyst fragments of the transition state in the text). The transition-state stabilization through interaction between catalytic fragments, as demonstrated by the interaction/distortion model, clearly outperforms destabilization incurred due to the distortion of catalytic fragments and hence is recognized as a major factor contributing to the high stereoselectivity of reaction. Furthermore, the metal-enamine interaction described through the Cu···C7 distance is identified as a vital noncovalent interaction at the transition state. Our calculations show that the catalytic (covalent) activations and metal-enamine interaction can operate in tandem to amplify the net interaction between two catalytic fragments. The cooperative nature of these interactions is also reflected in the trend of interaction energies, which show a large variation with a subtle change in the metal-enamine interaction. Our computational model verified for the different catalytic combinations of chiral amine and Cu catalysts successfully rationalizes the experimentally observed enantioselectivity.
我们描述了一类涉及手性胺和 Cu 催化剂协同作用的有趣反应的计算研究。使用密度泛函理论方法研究了醛的对映选择性α-烯丙基化反应中立体选择性决定步骤，以深入了解产物选择性的起源。我们发现，反应物以烯胺和烯基 Cu(III)中间体的形式进行催化活化，通过在过渡态（在文本中称为过渡态中的烯胺和 Cu 催化剂片段）中改善这两种中间体之间的相互作用，显著降低了加成步骤的活化能垒。通过催化片段之间的相互作用来稳定过渡态，正如相互作用/变形模型所证明的那样，明显优于由于催化片段的变形而引起的失稳，因此被认为是导致反应高立体选择性的主要因素。此外，通过 Cu···C7 距离描述的金属-烯胺相互作用被确定为过渡态中至关重要的非共价相互作用。我们的计算表明，催化（共价）活化和金属-烯胺相互作用可以协同作用，放大两个催化片段之间的净相互作用。这些相互作用的协同性质也反映在相互作用能的趋势上，它随着金属-烯胺相互作用的细微变化而有很大的变化。我们的计算模型成功地验证了不同手性胺和 Cu 催化剂的催化组合，合理地解释了实验观察到的对映选择性。
