title: A Dual-Catalysis Anion-Binding Approach to the Kinetic Resolution of Amines: Insights into the Mechanism via a Combined Experimental and Computational Study.
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.
authors: ‡Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
authors: Nisha
authors: N
authors: Mittal
authors: #Institute of Organic Chemistry, Justus-Liebig University, Heinrich-Buff-Ring 58, 35392 Giessen, Germany.
authors: Katharina M
authors: KM
authors: Lippert
authors: ‡Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
authors: Chandra Kanta
authors: CK
authors: De
authors: ‡Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
authors: Eric G
authors: EG
authors: Klauber
authors: ‡Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
authors: Thomas J
authors: TJ
authors: Emge
authors: #Institute of Organic Chemistry, Justus-Liebig University, Heinrich-Buff-Ring 58, 35392 Giessen, Germany.
authors: Peter R
authors: PR
authors: Schreiner
authors: ‡Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
authors: Daniel
authors: D
authors: Seidel