A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric Phase-Transfer Catalysts. Application of Quantitative Structure Activity/Selectivity Relationships

• Published in: Journal of organic chemistry 2011-06, Vol.76 (11), p.4337-4357
• Main Authors: Denmark, Scott E, Gould, Nathan D, Wolf, Larry M
• Format: Article
• Language: English
• Subjects: Alkylation; Catalysis; Catalysts: preparations and properties; Chemistry; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Kinetics; Kinetics and mechanisms; Models, Molecular; Molecular Conformation; Organic chemistry; Preparations and properties; Quantitative Structure-Activity Relationship; Quaternary Ammonium Compounds - chemical synthesis; Quaternary Ammonium Compounds - chemistry; Reactivity and mechanisms; Stereoisomerism; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Thermodynamics
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo2005457

Although the synthetic utility of asymmetric phase-transfer catalysis continues to expand, the number of proven catalyst types and design criteria remains limited. At the origin of this scarcity is a lack in understanding of how catalyst structural features affect the rate and enantioselectivity of phase transfer catalyzed reactions. Described in this paper is the development of quantitative structure−activity relationships (QSAR) and −selectivity relationships (QSSR) for the alkylation of a protected glycine imine with libraries of quaternary ammonium ion catalysts. Catalyst descriptors including ammonium ion accessibility, interfacial adsorption affinity, and partition coefficient were found to correlate meaningfully with catalyst activity. The physical nature of the descriptors was rationalized through differing contributions of the interfacial and extraction mechanisms to the reaction under study. The variation in the observed enantioselectivity was rationalized employing a comparative molecular field analysis (CoMFA) using both the steric and electrostatic fields of the catalysts. A qualitative analysis of the developed model reveals preferred regions for catalyst binding to afford both configurations of the alkylated product.