Department of Theoretical Chemistry, School of Biotechnology, Royal Institute of Technology, SE-10691 Stockholm, Sweden.
J Org Chem. 2010 Jul 16;75(14):4728-36. doi: 10.1021/jo100488g.
The intramolecular aldol reaction of acyclic ketoaldehydes catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is investigated using density functional theory calculations. Compared to the proline-catalyzed aldol reaction, the use of TBD provides a unique and unusual complete switch of product selectivity. Three mechanistic pathways are proposed and evaluated. The calculations provide new insights into the activation mode of bifunctional guanidine catalysts. In the favored mechanism, TBD first catalyzes the enolization of the substrate and then the C-C bond formation through two concerted proton transfers. In addition, the computationally predicted stereochemical outcome of the reaction is in agreement with the experimental findings.
本文使用密度泛函理论计算研究了 1,5,7-三氮杂二环[4.4.0]癸-5-烯（TBD）催化的非环酮醛的分子内羟醛反应。与脯氨酸催化的羟醛反应相比，使用 TBD 提供了独特且不寻常的完全产物选择性切换。提出并评估了三种反应机理。该计算为双功能胍催化剂的活化模式提供了新的见解。在有利的机理中，TBD 首先催化底物的烯醇化，然后通过两个协同质子转移进行 C-C 键形成。此外，反应的计算预测的立体化学结果与实验结果一致。
