Studies On Asymmetric Catalysis Of Chiral Ionic Liquid Derived From Proline

Chiral ionic liquids (CILs) have recently emerged as a hot research focus because of their fascinating and characteristic properties. Due to their facile chemical modification, ILs with chiral cations derived from amino acid especially (S)-proline were successfully utilized as highly enantioselective organocalaysts, while there are only a few CILs modified on the anion structure.Our research focused on the catalytic properties of [EMIm][Pro] which was developed by Ohno. We had successfully introdued CILs modified on the anion structure as catalyst into asymmetric organic reactions for the first time. What’s more, the application scope of proline modified CIL [EMIm][Pro] was expanded and asymmetric Michael addition, asymmetric Aldol reacton, asymmetric Mannich reaction toghther with asymmetric multicomponent cascade reaction were tested for catalyst [EMIm][Pro] with good results.In the current work, a mild and efficient procedure for Michael additions of cyclohexanone to chalcones has been developed. In the presence of amino acid ionic liquid [EMIm][Pro] (200 mol%), cyclohexanone reacted with various chalcones to afford Michael adducts in high yields (85-98%) and moderate to good enantioselectivities (16-94% ee), accompanied by an unexpected solvent-dependent inversion of the enantioselectivity.Next, we have applied [EMIm][Pro] as a green and efficient organocatalyst for direct asymmetric aldol reactions. When 30 mol% of catalyst loading was used, corresponding aldol products with moderate to excellent yields (up to 99%), low to high diastereoselectivities (up to 97:3) and good to excellent enantiomeric excesses (up to 99%) were afforded. As [BMIm]BF4 was used as solvent, a green and efficient system was developed and could be reused for 4 runs with a slight reduction in activity.As a continuation of our work, a novel one-pot three-component asymmetric Mannich reaction using [EMIm][Pro] as a catalyst has been developed. By employing this new reaction system, a variety of optically activeβ-amino carbonyl compounds were synthesized in up to 99% yield with up to 99 dr and 99% ee.An amino acid ionic liquid [EMIm][Pro] catalyzed asymmetric one-pot multicomponent cascade process for efficient synthesis of tetrahydropyridines was also developed. The reaction with catalyst loading as low as 5 mol% proceeded smoothly with good to excellent diastereo- and enantioselectivity in the presence of water. The multicomponent cascade process was consisted of imine formation, Mannich reaction and an intramolecular cyclization.We also found that an ionic liquid [EMIm][CF3C00] proved to be an efficient additive for proline-catalyzed direct asymmetric aldol reactions between cyclic ketones and aromatic aldehydes in [BMIm]BF4 at room temperature. Corresponding aldol products in low to good yields (trace-93%) and excellent enantiomeric excesses (up to 98%) were afforded. Recycling of the catalyst and additive together with the solvent ([BMIm]BF4) was possible up to 5 runs with only slight reduction in activity.