Enantioselective synthesis and physicochemical properties of libraries of 3-amino- and 3-amidofluoropiperidines
| Autor: | Santosh S. Kulkarni, Domingo Gomez Pardo, Aurelie Orliac, Wolfgang H. B. Sauer, Julie Routier, Agnes Bombrun, Janine Cossy, Fabienne Burgat Charvillon |
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| Rok vydání: | 2013 |
| Předmět: |
Magnetic Resonance Spectroscopy
Hydrocarbons Fluorinated Molecular Structure Stereochemistry Organic Chemistry Enantioselective synthesis chemistry.chemical_element Protonation Stereoisomerism General Chemistry Ring (chemistry) Catalysis chemistry.chemical_compound chemistry Piperidines Lipophilicity Fluorine Combinatorial Chemistry Techniques Piperidine |
| Zdroj: | Chemistry (Weinheim an der Bergstrasse, Germany). 20(13) |
| ISSN: | 1521-3765 |
| Popis: | The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pKa due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H(+) and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pKa between cis- and trans-3-amino-5-fluoropiperidines. |
| Databáze: | OpenAIRE |
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