116574-75-5Relevant articles and documents
Understanding the Conformational Behavior of Fluorinated Piperidines: The Origin of the Axial-F Preference
Nairoukh, Zackaria,Strieth-Kalthoff, Felix,Bergander, Klaus,Glorius, Frank
, p. 6141 - 6146 (2020)
Gaining an understanding of the conformational behavior of fluorinated compounds would allow for expansion of the current molecular design toolbox. In order to facilitate drug discovery efforts, a systematic survey of a series of diversely substituted and protected fluorinated piperidine derivatives has been carried out using NMR spectroscopy. Computational investigations reveal that, in addition to established delocalization forces such as charge–dipole interactions and hyperconjugation, solvation and solvent polarity play a major role. This work codifies a new design principle for conformationally rigid molecular scaffolds.
Accessing (Multi)Fluorinated Piperidines Using Heterogeneous Hydrogenation
Bergander, Klaus,Daniliuc, Constantin G.,Glorius, Frank,Heusler, Arne,Nairoukh, Zackaria,Wagener, Tobias
, p. 12052 - 12057 (2020/11/27)
Fluorinated piperidines are desirable motifs for pharmaceutical and agrochemical research. Nevertheless, general synthetic access remains out of reach. Herein, we describe a simple and robust cis-selective hydrogenation of abundant and cheap fluoropyridines to yield a broad scope of (multi)fluorinated piperidines. This protocol enables the chemoselective reduction of fluoropyridines while tolerating other (hetero)aromatic systems using a commercially available heterogenous catalyst. Fluorinated derivatives of important drug compounds are prepared, and a straightforward strategy for the synthesis of enantioenriched fluorinated piperidines is disclosed.
