NMR Structure Determination of Ion Pairs Derived from Quinine:  A Model for Templating in Asymmetric Phase-Transfer Reductions by BH₄^- with Implications for Rational Design of Phase-Transfer Catalysts

Abstract

The solution structures of ion pairs formed by quarternary ammonium ions derived from quinine alkaloid with small hard anions (BH(4)(-) or Cl(-)) in CDCl(3) have been characterized by nuclear magnetic resonance methods. Structural observations have been correlated with the sense of asymmetric induction observed in the phase-transfer reduction of 9-anthryl trifluoromethyl ketone by borohydride (BH(4)(-)) when catalyzed by the quaternary N-benzylquinine ammonium ion. From interionic nuclear Overhauser effects (NOEs), it appears that the BH(4)(-) ion occupies two of the four trigonal pyramidal sites formed by substituents of the quarternary nitrogen of the catalyst cation. One of these sites is in close proximity to the cation's hydroxyl group that is strictly required for asymmetric induction in the model reaction, while the other site is near the vinyl group on the cation. The vinyl group does not appear to be important for determining the sense or extent of asymmetric induction. Using energy-minimized structures derived from NMR data, it was predicted that the N-(9-methyleneanthryl)quinine-quarternary ammonium catalyst would give improved asymmetric induction in the model reaction due to a preferred anion occupancy at the site near the hydroxyl group. An improvement in enantiomeric excess (ee) is observed using the anthryl-modified catalyst, and NMR studies on the modified catalyst confirm the predicted change in anion binding site occupancies. The changes in site occupancies determined by NMR can be fitted to a simple kinetic model that correctly predicts the extent of change in ee.

Asymmetric Ion‐Pairing Catalysis

“…26 Pochapsky and co-workers provided experimental support for preferred anion occupancy at this face of the ammonium ion with the observation of specific interionic NOE correlations of a cinchona alkaloid-derived ammonium• borohydride ion pair in solution. [15] The higher selectivity observed with the N -anthracenylmethyl catalysts 1c – d versus N -benzyl catalyst 1b is attributed to more effective differentiation of the tetrahedron faces.…”

Asymmetrische Ionenpaarkatalyse

“…Anschließend machten sich Park und Jew den positiven Einfluss sterisch anspruchsvoller N(1)-Substituenten für die Entwicklung dimerer und trimerer, von Cinchona-Alkaloiden abstammender Katalysatoren zu Nutze, die über das Chinuclidinium-Stickstoffatom miteinander verknüpft sind. [15] Die mit den N-Anthracenylmethylkatalysatoren 1 c,d beobachtete und im Vergleich zu dem N-Benzylkatalysator 1 b hçhere Selektivität ist einer effektiveren Differenzierung der Tetraederflächen zuzuschreiben. [5e] Die Grundlage für die Enantioselektivität in der durch die N-Anthracenylmethylammoniumsalze 1 c und 1 d katalysierten Alkylierung des Glycinderivats 4 wurde von mehreren Forschungsgruppen untersucht.…”

Heteronuclear NOE Spectroscopy of Ionic Liquids

“…[14] Several groups were already able to demonstrate the usefulness of NOE spectroscopy for the investigation of ion pairs, particularly for metal complexes in solution. [15][16][17][18][19][20] Consequently, the next step was the investigation of ILs in solution through NOE spectroscopy. Dupont was the first to apply homonuclear H,H HOESY NMR spectroscopy on ionic liquids in organic solvents to study ion pairing.…”