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A Dual-Catalysis Anion-Binding Approach to the Kinetic Resolution of Amines: Insights into the Mechanism via a Combined Experimental and Computational Study

Author:
Mittal, Nisha, Lippert, Katharina M., De, Chandra Kanta, Klauber, Eric G., Emge, Thomas J., Schreiner, Peter R., Seidel, Daniel
Source:
Journal of the American Chemical Society 2015 v.137 no.17 pp. 5748-5758
ISSN:
1520-5126
Subject:
amines, catalysts, chemical reactions, models, solvents
Abstract:
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.
Agid:
5410010