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Mechanochemically Activated Asymmetric Organocatalytic Domino Mannich Reaction-Fluorination

Dominika Krištofíková, Mária Mečiarová, Erik Rakovský, Radovan Šebesta

2020ACS Sustainable Chemistry & Engineering53 citationsDOI

Abstract

Mechanochemical activation effectively mediated asymmetric organocatalytic domino Mannich addition followed by diastereoselective fluorination. The Mannich reactions of pyrazolones and to a lesser extent those of isoxazolones were effective under solvent-free ball-milling conditions. This reaction in combination with a chiral squaramide catalyst provided corresponding products in high yields and enantiomeric purities up to 99:1 e.r. and as a single diastereomer. DFT calculations revealed reasons for high diastereoselectivity.

Topics & Concepts

SquaramideMannich reactionDiastereomerChemistryOrganocatalysisCatalysisDominoEnantiomerCascade reactionOrganic chemistryEnantioselective synthesisBall millSolventCombinatorial chemistryMaterials scienceComposite materialFluorine in Organic ChemistryAsymmetric Synthesis and CatalysisSynthesis and Reactions of Organic Compounds