Institute of Organic Chemistry, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
Department of Physical and Theoretical Chemistry, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
Angew Chem Int Ed Engl. 2023 Jul 3;62(27):e202301183. doi: 10.1002/anie.202301183. Epub 2023 May 23.
Chiral phosphoric acids (CPA) have become a privileged catalyst type in organocatalysis, but the selection of the optimum catalyst is still challenging. So far hidden competing reaction pathways may limit the maximum stereoselectivities and the potential of prediction models. In CPA-catalyzed transfer hydrogenation of imines, we identified for many systems two reaction pathways with inverse stereoselectivity, featuring as active catalyst either one CPA or a hydrogen bond bridged dimer. NMR measurements and DFT calculations revealed the dimeric intermediate and a stronger substrate activation via cooperativity. Both pathways are separable: Low temperatures and high catalysts loadings favor the dimeric pathway (ee up to -98 %), while low temperatures with reduced catalyst loading favor the monomeric pathway and give significantly enhanced ee (92-99 % ee; prior 68-86 % at higher temperatures). Thus, a broad impact is expected on CPA catalysis regarding reaction optimization and prediction.
手性磷酸（CPA）已成为有机催化中一种重要的催化剂类型，但选择最佳催化剂仍然具有挑战性。到目前为止，隐藏的竞争反应途径可能限制了最大立体选择性和预测模型的潜力。在 CPA 催化的亚胺转移氢化中，我们为许多体系确定了两种具有相反立体选择性的反应途径，其活性催化剂要么是一种 CPA，要么是氢键桥联二聚体。NMR 测量和 DFT 计算揭示了二聚体中间体和通过协同作用增强的底物活化。这两种途径是可分离的：低温和高催化剂负载有利于二聚体途径（ee 高达-98%），而低温和降低催化剂负载有利于单体途径，并显著提高 ee（92-99%ee；之前在较高温度下为 68-86%ee）。因此，这预计将对 CPA 催化的反应优化和预测产生广泛影响。
