【摘要】 采用M06-2X/6-311+G**对手性磷酸催化的4-氯-N-（2-（3’-羟基-1’-苯基螺[环戊烷-1,2’-吲哚啉]-3’-基）乙基）（1a）的不对称氮杂频哪醇重排反应进行了深入的机理研究。计算结果表明，整个催化循环经历底物1a脱水、对映选择性的氮杂频哪醇重排、分子内环化和催化剂再生得到吲哚啉产物。氮杂频哪醇重排是该反应的关键立体控制步骤。手性催化剂通过双官能团手性磷酸和氮杂邻二甲苯中间体之间的2个结合位点控制了对映选择性步骤过渡态的取向。重要的是，理论研究表明底物和手性催化剂的中心官能团上的氧阴离子和臂之间形成的多个C—H···π，C—H···O和C—H···N氢键和N—H···O^-静电相互作用在决定立体化学结果方面起着关键作用。主要过渡态中强的N—H···O^-相互作用提高了对映选择性。此外，对映选择性过渡态之间6.3 kJ·mol^-1的能量差所对应的ee值为89%，与实验结果90%非常吻合。更多还原

【Abstract】 A comprehensive mechanistic study on the chiral phosphoric acid catalyzed an enantioselective asymmetric aza-pinacol rearrangement of 4-chloro-N-（2-（3’-hydroxy-1’-phenylspiro[cyclopentane-1,2’-indolin]-3’-yl）ethyl）（1a） is investigated at the M06-2X/6-311+G（d,p） level. Our computational results suggest that the whole catalytic cycle proceeds through dehydration of1a, enantioselective aza-pinacol rearrangement, intramolecular cyclization and catalyst regeneration to deliver the fused indoline product. The aza-pinacol rearrangement is the key stereocontrolling step of the title reaction. The chiral catalyst controls the orientation of the transition states of the enantioselective step through two potential binding sites between the bifunctional chiral phosphate and the aza-ortho-xylylene intermediate. Moreover, theoretical studies identified that the multiple C—H···π, C—H···O, and C—H···N hydrogen bonds and N—H···O^–electrostatic interactions between the substrates and the arms as well as functional oxygen anion of the chiral catalyst（R）-4c play a crucial role in determining the stereochemical outcomes. And the strong N—H···O^–interaction in the major transition state was found to contribute to the high levels of enantioselectivity. Additionally, the predicted enantiomeric excess（ee） of 89% based on the 6.3 kJ·mol^–1energy difference between the enantioselective TS-2-major and TS-2-minor is in agreement with the experimental results of 90%.更多还原