Harden Ingolf, Neese Frank, Bistoni Giovanni
Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm Platz 1 45470 Mülheim an der Ruhr Germany.
Department of Chemistry, Biology and Biotechnology, University of Perugia Via Elce di Sotto, 8 06123 Perugia Italy
Chem Sci. 2023 Sep 18;14(38):10580-10590. doi: 10.1039/d3sc03769j. eCollection 2023 Oct 4.
The formation of Brønsted acid aggregates in the course of asymmetric organocatalytic reactions is often overlooked in mechanistic studies, even though it might have a deep impact on the stereo-controlling factors of the transformations. In this work, we shed light on the influence of the catalyst structure and reaction conditions on the spontaneity of the aggregation process for popular chiral organocatalysts derived from phosphoric acids using high-level quantum mechanical calculations. Our study encompasses small and sterically unhindered chiral phosphoric acids as well as large and "confined" imidodiphosphates and imidodiphosphorimidates. These systems have recently proven particularly effective in promoting a large number of highly relevant asymmetric transformations. While cooperative catalytic effects of sterically less hindered chiral phosphoric acid catalysts are well appreciated in literature, it is found that the formation of catalyst dimers in solution is possible for both standard and confined catalysts. The spontaneity of the aggregation process depends on reaction conditions like solvent polarity, polarizability, temperature, the nature of the interaction with the substrate, as well as the catalyst architecture. Finally, it is shown that, at low temperatures (153 K), the aggregation process can profoundly influence the reaction kinetics and selectivity.
在不对称有机催化反应过程中，布朗斯特酸聚集体的形成在机理研究中常常被忽视，尽管它可能对转化反应的立体控制因素产生深远影响。在这项工作中，我们利用高水平量子力学计算，揭示了催化剂结构和反应条件对源自磷酸的常见手性有机催化剂聚集过程自发性的影响。我们的研究涵盖了体积小且空间位阻小的手性磷酸以及体积大且“受限”的亚氨基二磷酸酯和亚氨基二磷酰亚胺。这些体系最近已被证明在促进大量高度相关的不对称转化反应中特别有效。虽然空间位阻较小的手性磷酸催化剂的协同催化作用在文献中已得到充分认识，但发现无论是标准催化剂还是受限催化剂，在溶液中都有可能形成催化剂二聚体。聚集过程的自发性取决于反应条件，如溶剂极性、极化率、温度、与底物相互作用的性质以及催化剂结构。最后表明，在低温（153 K）下，聚集过程会深刻影响反应动力学和选择性。
