Pd/C‐Catalyzed Hydrogenation of CF <sub>3</sub> ‐, CF <sub>2</sub> H‐, and CF <sub>2</sub> CO <sub>2</sub> Et‐containing Pyridines: A Robust Method for Highly Functionalized containing Piperidines
Abstract
ABSTRACT A robust method for the hydrogenation of various pyridines substituted by CF 3 , CF 2 H, and CF 2 CO 2 Et groups has been developed. Using an inexpensive heterogeneous Pd/C catalyst, diversely functionalized fluorinated piperidines were synthesized under air‐ and moisture‐tolerant reaction conditions (37 examples, up to 98% yield) with good to high diastereoselectivity. Comprehensive NMR studies enabled full structural characterization of the synthesized fluorinated compounds. The synthetic utility of the methods was further highlighted by the gram‐scale preparation of the fluorinated scaffolds and the synthesis of a trifluoromethylated analog of the antipsychotic drug melperone.
Article Details
Authors (8)
Thibaud Charvillat
INSA Rouen Normandie, Univ Rouen Normandie, Univ Caen Normandie, ENSICAEN, CNRS Institut CARMeN (UMR 6064) Rouen France
Patrick Bernardelli
Sanofi R&D, 13 Quai Jules Guesde Vitry Sur Seine France
Marc Daumas
Responsable De C&BD Science & innovation Sanofi‐Aventis R&D, 371 Rue Du Prof. J. Blayac Montpellier France
Xavier Pannecoucke
INSA Rouen Normandie, Univ Rouen Normandie, Univ Caen Normandie, ENSICAEN, CNRS Institut CARMeN (UMR 6064) Rouen France
Vincent Ferey
Sanofi Winthrop Industrie/MSAT/ Site d'aramon Route d'Avignon Aramon France
Hassan Oulyadi
INSA Rouen Normandie, Univ Rouen Normandie, Univ Caen Normandie, ENSICAEN, CNRS Institut CARMeN (UMR 6064) Rouen France
Muriel Sebban
INSA Rouen Normandie, Univ Rouen Normandie, Univ Caen Normandie, ENSICAEN, CNRS Institut CARMeN (UMR 6064) Rouen France
Tatiana Besset
INSA Rouen Normandie, Univ Rouen Normandie, Univ Caen Normandie, ENSICAEN, CNRS Institut CARMeN (UMR 6064) Rouen France