Franta Maximilian, Pattanaik Aryaman, Silva Wagner, Motiram-Corral Kumar, Rehbein Julia, Gschwind Ruth M
Institute of Organic Chemistry, University Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
J Am Chem Soc. 2025 Jan 22;147(3):2549-2558. doi: 10.1021/jacs.4c14096. Epub 2025 Jan 9.
In ion-pair catalysis, the last intermediate structures prior to the stereoselective transition states are of special importance for predictive models due to the high isomerization barrier between - and -substrate double bonds connecting ground and transition state energies. However, in prior experimental investigations of chiral phosphoric acids (CPA) solely the early intermediates could be investigated while the key intermediate remained elusive. In this study, the first experimental structural and conformational insights into ternary complexes with CPAs are presented using a special combination of low temperature and relaxation optimized N HSQC-NOESY NMR spectroscopy to enhance sensitivity. Combined NMR investigations and theoretical calculations revealed three conformers of the ternary complex, of which one also closely resembles the previously calculated transition states. In addition, a 2:1:1 ternary complex as well as an unprecedent [3:3] dimeric species consisting of two ternary complexes was revealed. Given the importance of the ground state energies for the transition state interpretation in ion pair catalysis we believe that the presented experimental insight into the structural and conformational variety of the ternary complexes is a key to the future development of predictive models in ion pair catalysis.
在离子对催化中，由于连接基态和过渡态能量的α-和β-底物双键之间存在较高的异构化势垒，立体选择性过渡态之前的最后中间结构对于预测模型尤为重要。然而，在之前对手性磷酸（CPA）的实验研究中，只能研究早期中间体，而关键中间体仍然难以捉摸。在本研究中，通过低温和弛豫优化的N HSQC-NOESY NMR光谱的特殊组合提高灵敏度，首次展示了对与CPA形成的三元复合物的结构和构象的实验见解。结合NMR研究和理论计算揭示了三元复合物的三种构象，其中一种也与先前计算的过渡态非常相似。此外，还发现了一种2:1:1的三元复合物以及一种由两个三元复合物组成的前所未有的[3:3]二聚体物种。鉴于基态能量对于离子对催化中过渡态解释的重要性，我们认为所展示的对三元复合物结构和构象多样性的实验见解是离子对催化预测模型未来发展的关键。
