Stereoselective Access to Fluorinated and Non‐fluorinated Quaternary Piperidines: Synthesis of Pipecolic Acid and Iminosugar Derivatives |
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| Authors: | Prof?Dr Santos Fustero Dr Laia Albert Natalia Mateu Dr Gema Chiva Javier Miró Prof?Dr Javier González Dr José Luis Aceña |
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| Institution: | 1. Departmento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia (Spain), Fax: (+34)?963544939;2. Laboratorio de Moléculas Orgánicas, Centro de Investigación Príncipe Felipe, 46012 Valencia (Spain), Fax: (+34)?963289701;3. Departmento de Química Orgánica e Inorgánica, Universidad de Oviedo, 33071 Oviedo (Spain);4. New address: Departamento de Química Orgánica I, Universidad del País Vasco, 20018 San Sebastián (Spain) |
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| Abstract: | 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 (TMSCF3) followed by iodoamination and migration of the CF3 group allowed access to four derivatives of α‐(trifluoromethyl)pipecolic acid. A theoretical study of the CF3‐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. |
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| Keywords: | amino acids density functional calculations fluorine iminosugars quaternary stereocenters |
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