‡Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
#Institute of Organic Chemistry, Justus-Liebig University, Heinrich-Buff-Ring 58, 35392 Giessen, Germany.
J Am Chem Soc. 2015 May 6;137(17):5748-58. doi: 10.1021/jacs.5b00190. Epub 2015 Apr 23.
Racemic benzylic amines undergo kinetic resolution via benzoylation with benzoic anhydride in the presence of a dual catalyst system consisting of a readily available amide-thiourea catalyst and 4-dimethylaminopyridine (DMAP). An evaluation of various experimental parameters was performed in order to derive a more detailed understanding of what renders this process selective. The catalyst's aggregation behavior and anion-binding ability were evaluated in regard to their relevance for the catalytic process. Alternate scenarios, such as catalyst deprotonation or the in situ formation of a neutral chiral acylating reagent were ruled out. Detailed computational studies at the M06/6-31G(d,p) level of theory including solvent modeling utilizing a polarized continuum model provide additional insights into the nature of the ion pair and reveal a range of important secondary interactions that are responsible for efficient enantiodiscrimination.
外消旋苄基胺在双催化剂体系（由易得的酰胺-硫脲催化剂和 4-二甲氨基吡啶（DMAP）组成）的存在下，与苯甲酸酐进行苯甲酰化反应，从而发生动力学拆分。为了更深入地了解使该过程具有选择性的原因，对各种实验参数进行了评估。评估了催化剂的聚集行为和阴离子结合能力，以了解它们与催化过程的相关性。排除了其他方案，如催化剂去质子化或原位形成中性手性酰化试剂。在 M06/6-31G(d,p)水平的理论上包括使用极化连续模型进行溶剂建模的详细计算研究，为离子对的性质提供了更多的见解，并揭示了一系列重要的次级相互作用，这些相互作用负责有效的对映体选择性。
