Pd/C‐Catalyzed Hydrogenation of CF 3 ‐, CF 2 H‐, and CF 2 CO 2
Thibaud Charvillat, Patrick Bernardelli, Marc Daumas, Xavier Pannecoucke, Vincent Ferey, Hassan Oulyadi, Muriel Sebban, Tatiana BessetABSTRACT
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.