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Stereoselective Access to Fluorinated and Non‐fluorinated Quaternary Piperidines: Synthesis of Pipecolic Acid and Iminosugar Derivatives
Author(s) -
Fustero Santos,
Albert Laia,
Mateu Natalia,
Chiva Gema,
Miró Javier,
González Javier,
Aceña José Luis
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201102351
Subject(s) - iminosugar , chemistry , pipecolic acid , dihydroxylation , stereoselectivity , trifluoromethyl , metathesis , alkylation , stereochemistry , enantioselective synthesis , combinatorial chemistry , alkyl , organic chemistry , amino acid , catalysis , enzyme , biochemistry , polymer , polymerization
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.