Stereoselective Access to Fluorinated and Non‐fluorinated Quaternary Piperidines: Synthesis of Pipecolic Acid and Iminosugar Derivatives

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.