6533b7dcfe1ef96bd12720d6
RESEARCH PRODUCT
The role of fluorine in the stereoselective tandem Aza-Michael addition to acrylamide acceptors: An experimental and theoretical mechanistic study
Santos FusteroAntonio Morán RamallalJavier GonzálezAlessandro VolonterioJulio PieraGema ChivaMatteo Zandasubject
Steric effectsModels MolecularReaction mechanismMagnetic Resonance SpectroscopyStereochemistrychemistry.chemical_elementStereoisomerismCatalysisMass Spectrometrychemistry.chemical_compoundComputational chemistrycalculationsReactivity (chemistry)density functionalAcrylamideTrifluoromethyldiastereoselectivity fluorine chemistryOrganic ChemistryStereoisomerismGeneral ChemistryFluorinechemistryFluorineMichael reactionpeptidesStereoselectivityMichael reactiondescription
Aza-Michael additions of alpha-amino esters to fluorinated acceptors take place in a highly stereoselective manner, to give partially modified Psi-[NHCH2]retropeptides incorporating a hydrolytically stable trifluoroalanine mimic. The reaction mechanism has been investigated experimentally and theoretically, in order to explain the effect of the trifluoromethyl group on the reactivity and the origins of the experimentally observed stereocontrol. The reaction is a two-step process, involving a tandem aza-Michael addition followed by a stereoselective hydrogen transfer. Both steps are base-catalyzed. The high level of stereocontrol is the result of a combination of electrostatic interactions and steric effects.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-01-01 |