Accessing (Multi)Fluorinated Piperidines Using Heterogeneous Hydrogenation

ACS Catal. 2020 Oct 16;10(20):12052-12057. doi: 10.1021/acscatal.0c03278. Epub 2020 Sep 18.

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.