Vermeeren Pascal, Hamlin Trevor A, Bickelhaupt F Matthias, Fernández Israel
Department of Theoretical Chemistry, Amsterdam Institute of, Molecular and Life Sciences (AIMMS), Amsterdam Center for, Multiscale Modeling (ACMM), Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081, HV, Amsterdam, The Netherlands.
Institute for Molecules and Materials (IMM), Radboud University, Heyendaalseweg 135, 6525, AJ, Nijmegen, The Netherlands.
Chemistry. 2021 Mar 17;27(16):5180-5190. doi: 10.1002/chem.202004496. Epub 2021 Jan 12.
The selectivity and rate enhancement of bifunctional hydrogen bond donor-catalyzed Diels-Alder reactions between cyclopentadiene and acrolein were quantum chemically studied using density functional theory in combination with coupled-cluster theory. (Thio)ureas render the studied Diels-Alder cycloaddition reactions exo selective and induce a significant acceleration of this process by lowering the reaction barrier by up to 7 kcal mol . Our activation strain and Kohn-Sham molecular orbital analyses uncover that these organocatalysts enhance the Diels-Alder reactivity by reducing the Pauli repulsion between the closed-shell filled π-orbitals of the diene and dienophile, by polarizing the π-orbitals away from the reactive center and not by making the orbital interactions between the reactants stronger. In addition, we establish that the unprecedented exo selectivity of the hydrogen bond donor-catalyzed Diels-Alder reactions is directly related to the larger degree of asynchronicity along this reaction pathway, which is manifested in a relief of destabilizing activation strain and Pauli repulsion.
使用密度泛函理论结合耦合簇理论，对双功能氢键供体催化的环戊二烯与丙烯醛之间的狄尔斯-阿尔德反应的选择性和速率增强进行了量子化学研究。（硫）脲使所研究的狄尔斯-阿尔德环加成反应具有外型选择性，并通过将反应势垒降低多达7 kcal mol 来显著加速这一过程。我们的活化应变和科恩-沙姆分子轨道分析表明，这些有机催化剂通过降低二烯和亲双烯体的闭壳层填充π轨道之间的泡利排斥、使π轨道远离反应中心，而不是通过增强反应物之间的轨道相互作用，来提高狄尔斯-阿尔德反应活性。此外，我们确定，氢键供体催化的狄尔斯-阿尔德反应前所未有的外型选择性与该反应途径上更大程度的异步性直接相关，这表现为不稳定的活化应变和泡利排斥的缓解。
