Polymer-supported thiourea catalysts for enantioselective Michael reaction

Abstract

Among the large number of reactions involving the formation of carbon-carbon bond, the addition of ketones to nitroolefins is a powerful tool for the synthesis of γ-nitro-carbonyl compounds, useful intermediates for pharmaceutical industry. Our recently reported primary amine-thioureas based on tert-butyl esters of natural amino acids exhibit excellent performance for the Michael reaction of ketones with nitroolefins providing the products quantitatively and almost stereospecifically (>99% ee).1,2 Using this methodology, enantiopure baclofen and phenibut (analogs of GABA) have been synthesized.2 Polymer-supported organocatalysts constitute a great challenge for the Michael reaction. In the current study, we report the immobilization of amine-thiourea catalysts containing (1S,2S)- or (1R,2R)-diphenylethylenediamine and tert-butyl aspartate, on various polymer supports, either directly or through spacer units. The solidsupported catalysts evaluated in the reaction between acetone and β- nitrostyrene and highlighted the importance of the choice of the polymer as well as the presence of the spacer or not. The direct attachment of the primary amine-thiourea-aspartate to a crosslinked polystyrene-divinyl benzene resin containing a uniform distribution of aminomethyl groups provides a supported catalyst that affords the product of the reaction between acetone and β-nitrostyrene quantitatively and in high enantioselectivity (91% ee).