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 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.
Authors
- Vincent Ferey (ORCID: https://orcid.org/0000-0003-4118-3707)
- T. Charvillat (ORCID: https://orcid.org/0000-0003-4181-4310)
- Muriel Sebban (ORCID: https://orcid.org/0000-0002-7907-1092)
- Tatiana Besset (ORCID: https://orcid.org/0000-0003-4877-5270)
- Hassan Oulyadi (ORCID: https://orcid.org/0000-0001-5813-1482)
- Patrick Bernardelli
- Xavier Pannecoucke (ORCID: https://orcid.org/0000-0002-4598-7895)
- Marc Daumas
Institutions
- Centre National de la Recherche Scientifique (FR)
- Sanofi (France) (FR)
- Normandie Université (FR)
- Université de Rouen Normandie (FR)
- Institut National des Sciences Appliquées Rouen Normandie (FR)
Publication Details
- Journal
- Angewandte Chemie
- Published
- 2026-06-30
- DOI
- https://doi.org/10.1002/ange.4352204
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Sanofi
- Agence Nationale de la Recherche