REQUIMTE, CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
J Org Chem. 2012 Apr 6;77(7):3252-61. doi: 10.1021/jo300005e. Epub 2012 Mar 14.
The diastereo- and enantioselectivity obtained experimentally by Christmann in the amine-catalyzed intramolecular Diels-Alder reaction of α,β-unsaturated carbonylic compounds were fully rationalized using density functional theory methods at the PBE1PBE/6-311+G** level. A polarizable continuum model was used to describe solvent effects. The selectivity is induced in the cyclization step, and while the enantioselectivity results from the syn/anti orientation around the C-N enamine bond, the diastereoselectivity mainly results from the syn/anti configuration of the substituents in the forming cyclopentane ring. The remarkable reaction rate experimentally observed when an external protic acid is used is attributed to the strong decrease in the activation energy of all steps needed for the enamine formation, while the external acid marginally influences the cyclization step. When hydrogen-bond-donor catalysts are used, the formation of one hydrogen bond in the cyclization step inverts the configuration and reduces the selectivity. The different behavior between dialdehydes and ketoaldehydes is suggested to be resulting from different reaction rates in the catalyst elimination step.
克里斯曼（Christmann）在α,β-不饱和羰基化合物的胺催化的分子内 Diels-Alder 反应中实验获得的非对映选择性和对映选择性，通过密度泛函理论方法在 PBE1PBE/6-311+G**水平上得到了完全的合理化。使用极化连续体模型来描述溶剂效应。选择性诱导在环化步骤中，而对映选择性源于 C-N 烯胺键的顺/反取向，非对映选择性主要源于形成环戊烷环的取代基的顺/反构型。当使用外部质子酸时，实验中观察到的显著反应速率归因于烯胺形成所需的所有步骤的活化能的强烈降低，而外部酸对环化步骤的影响很小。当使用氢键供体催化剂时，在环化步骤中形成一个氢键会反转构型并降低选择性。建议二醛和酮醛之间的不同行为是由于催化剂消除步骤中的不同反应速率所致。
