Bifunctional Hydrogen Bond Donor‐Catalyzed Diels–Alder Reactions: Origin of Stereoselectivity and Rate Enhancement

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(−1). 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.