Tobias Wagener, Arne Heusler, Zackaria Nairoukh, Klaus Bergander, Constantin G. Daniliuc, and Frank Glorius. 2020. “Accessing (Multi)Fluorinated Piperidines Using Heterogeneous Hydrogenation.” ACS Catal. 2020, 10, 12052 – 12057. Publisher's Version Abstract
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.
Coralie Gelis, Arne Heusler, Zackaria Nairoukh, and Frank Glorius. 2020. “Catalytic Transfer Hydrogenation of Arenes and Heteroarenes.” Chem. Eur. J. 2020, 26, 14090 – 14094. Publisher's Version Abstract
Abstract Transfer hydrogenation reactions are of great interest to reduce diverse molecules under mild reaction conditions. To date, this type of reaction has only been successfully applied to alkenes, alkynes and polarized unsaturated compounds such as ketones, imines, pyridines, etc. The reduction of benzene derivatives by transfer hydrogenation has never been described, which is likely due to the high energy barrier required to dearomatize these compounds. In this context, we have developed a catalytic transfer hydrogenation reaction for the reduction of benzene derivatives and heteroarenes to form complex 3-dimensional scaffolds bearing various functional groups at room temperature without needing compressed hydrogen gas.
Zackaria Nairoukh, Felix Strieth-Kalthoff, Klaus Bergander, and Frank Glorius. 2020. “Understanding the Conformational Behavior of Fluorinated Piperidines: The Origin of the Axial-F Preference.” Chem. Eur. J. 2020, 26, 6141 – 6146. Publisher's Version Abstract
Abstract 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.