Ionic Liquids Derived From L-prolinol Catalyzed Asymmetric Michael Addition

In recent years, the asymmetric Michael addition reactions have draw muchattentions because it is one of the most important carbon-carbon bond-formingreactions in organic synthesis. Due to their particular advantage, organocatalystswithout metal have been attached great importance in the field of catalytic reaction.Among the various organocatalysts, L-prolinol derivatives have been demonstrated tomake up a successful class of organocatalysts.However, these organocatalysts have some drawbacks, such as: the great amountsof application, the narrow application range and the difficulty for recycling. Becauseof the particular properties of ILs, there will be some particular effects whenquaternary ammonium groups are introduced into L-prolinol derivatives. Therefore, aseries of these catalysts were designed and synthesized, which were used inasymmetric Michael additions.Firstly, a series of functionalized chiral ionic liquids were designed andsynthesized. The starting material was (S)-(2-hydroxymethyl)-pyrrolidine. Cbzprotected L-prolinol was obtained after reacting with benzyl carbonochloridate. Then,through the reaction between the corresponding product and methanesulfonyl chloride,(S)-benzyl-2-((methylsulfonyloxy)-methyl)pyrrolidine-1-carboxylate was produced.After the reaction with LiBr,(S)-benzyl2-(chloromethyl)-pyrrolidine-1-carboxylatewas provided, which could converted into (S)-benzyl2-((dimethylamino)methyl)pyrrolidine-1-carboxylate when stirred with Me2NH. Then reacted with a series ofhalohydrocarbon could give the corresponding quaternary alkylammonium. Whenreacted with H2catalysed by Pd-C, the Cbz-protection was removed and the targetcompounds were afforded.At last, the catalytic effects of those ionic liquids on the Michael addition ofcyclohexanone to trans-nitrostyrene were investigated. It was found that thesederivatives are highly efficient organocatalysts with high yields (up to96%), highenantioselectivies (up to99%ee), and high diastereoselectivies (up to97:3dr).A plausible transition state was proposed to explain the stereochemical results,and the structure-activity relationship of catalysts was studied. Furthermore, thosecatalysts could be recycled without remarkable loss of catalytic activity andstereoselectivity. When those catalysts were used to catalyze Michael addition ofcyclohexanone to Derivate of trans-nitrostyrene, they showed preferable results.