6533b86efe1ef96bd12cbe31
RESEARCH PRODUCT
Stereoselective Access to Fluorinated and Non-fluorinated Quaternary Piperidines: Synthesis of Pipecolic Acid and Iminosugar Derivatives
Javier GonzálezGema ChivaLaia AlbertJavier MiróJosé Luis AceñaNatalia MateuSantos Fusterosubject
HalogenationStereochemistryIminosugarAlkylationCatalysischemistry.chemical_compoundPiperidinesfluorineiminosugarsPipecolic acidchemistry.chemical_classificationamino acidsTrifluoromethylMolecular StructureChemistryOrganic ChemistryHalogenationStereoisomerismGeneral ChemistryImino SugarsDihydroxylationPipecolic Acidsdensity functional calculationsquaternary stereocentersStereoselectivityLactonedescription
The preparation of optically pure quaternary piperidines, both fluorinated and non-fluorinated, has been achieved from a chiral imino lactone derived from (R)-phenylglycinol. In the case of the fluorinated derivatives, the addition of (trifluoromethyl)trimethylsilane (TMSCF(3)) followed by iodoamination and migration of the CF(3) group allowed access to four derivatives of α-(trifluoromethyl)pipecolic acid. A theoretical study of the CF(3)-group rearrangement has been carried out to help establish the reaction mechanism of this uncommon transformation. Moreover, a route to trifluoromethyl-substituted iminosugars was also developed through the diastereoselective dihydroxylation of suitable synthetic intermediates. Conversely, alkylation of the starting substrate and subsequent cross-metathesis and aza-Michael reactions led to α-alkyl derivatives of the target compounds.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-01-01 |