Enantio- and Diastereoselective Michael Addition of Cyclic Ketones/Aldehydes to Nitroolefins in Water as Catalyzed by Proline-Derived Bifunctional Organocatalysts
Daeil Bae, Jin Won Lee, Do Hyun Ryu
Abstract
New l-proline-derived bifunctional secondary amine organocatalysts were synthesized for enantioselective Michael reactions in water as a solvent. Application of these catalysts in Michael additions provided high yield (up to 97%) with high stereoselectivity (dr up to 99:1 and ee up to 99%). The effect of phenyl group at (R)-C6 in the catalyst was investigated and played a key role in successful catalysis by density functional theory computational calculations. The synthetic utility of this reaction was demonstrated by the formal synthesis of Sch 50971, which is a novel histamine H3 receptor agonist.
Topics & Concepts
BifunctionalEnantioselective synthesisMichael reactionCatalysisChemistryStereoselectivityOrganocatalysisAmine gas treatingYield (engineering)ProlineOrganic chemistryMedicinal chemistryAmino acidMaterials scienceBiochemistryMetallurgyAsymmetric Synthesis and CatalysisChemical Synthesis and AnalysisSynthetic Organic Chemistry Methods