A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric Phase-Transfer Catalysts. Synthesis of Catalyst Libraries and Evaluation of Catalyst Activity

Abstract

Despite over three decades of research into asymmetric phase transfer catalysis (APTC), a fundamental understanding of the factors that affect the rate and stereoselectivity of this important process are still obscure. This paper describes the initial stages of a long-term program aimed at elucidating the physical organic foundations of APTC employing a chemoinformatic analysis of the alkylation of a protected glycine imine with a libraries of enantiomerically enriched quaternary ammonium ions. The synthesis of the quaternary ammonium ions follows a diversity oriented approach wherein the tandem inter[4+2]/intra[3+2] cycloaddition of nitroalkenes serves as the key transformation. A two part synthetic strategy comprised of: (1) preparation of enantioenriched scaffolds and (2) development of parallel synthesis procedures is described. The strategy allows for the facile introduction of four variable groups in the vicinity of a stereogenic quaternary ammonium ion. The quaternary ammonium ions exhibited a wide range of activity and to a lesser degree enantioselectivity. Catalyst activity and selectivity are rationalized in a qualitative way based on the effective positive potential of the ammonium ion.

Novel kinetics model for third-liquid phase-transfer catalysis system of the “complex” carbanion: Competitive role between catalytic cycles

“…QSAR is a useful method for understanding the relationship between physicochemical properties of reactant molecules and the reaction kinetics in PTC system [43,44]. Accordingly, linear free energy relationship (LFER) models with the molecular parameters -calculated partition coefficient between octanol and water (ClogP), the calculated volume (ClogV) [45], the number of carbon atoms (N m ) and the ''closest approach of the ion'' (''a c '') were evaluated.…”

New insights on reaction pathway selectivity promoted by crown ether phase-transfer catalysis: Model ab initio calculations of nucleophilic fluorination

“…For example, PTC is recognized as an important green chemistry procedure that reduces waste generation [1][2][3][4][5]. In the meantime, advances in the asymmetric version of PTC have also generated considerable interest because of potential applications in the industrial asymmetric synthesis of pharmaceuticals [6][7][8][9][10][11][12][13][14].…”

Multidimensional steric parameters in the analysis of asymmetric catalytic reactions

“…To generate predictive power, the small energetic differences in diastereomeric transition states (to which Knowles made reference) must be systematically scrutinized. Probing these transition states using physical organic and computational techniques has shed substantial light on the mechanisms of asymmetric induction, providing motivation for predictive catalyst design [2][3][4][5][6][7][8][9][10][11][12][13][14][15] . Specifically, recent reports using computational techniques for determining and defining non-covalent, attractive interactions in organocatalysis have provided insight for elucidating the key roles of these interactions in determining reactivity and enantioselectivity 4,[16][17][18][19] .…”