Functionalized Dialdehydes as Promising Scaffolds for Access to Heterocycles and β-Amino Acids: Synthesis of Fluorinated Piperidine and Azepane Derivatives

Functionalized dialdehydes are considered important substrates that can be transformed into various substituted heterocyclic, alicyclic, and polysubstituted compounds. Here, we report a robust stereocontrolled procedure for the synthesis of novel functionalized trifluoromethyl-containing piperidine and azepane derivatives, based on oxidative ring cleavage of the C=C bond of diversely substituted cycloalkenes, followed by reductive ring closure of the diformyl intermediates in the presence of fluorine-containing amines.

Stereocontrolled Synthesis of Fluorine-Containing Piperidine γ-Amino Acid Derivatives

Front Cover: Stereocontrolled Synthesis of Fluorine-Containing Piperidine γ-Amino Acid Derivatives (Eur. J. Org. Chem. 12/2019)

Synthesis of fluorinated piperidine and azepane β-amino acid derivatives

Abstract A convenient and robust stereocontrolled procedure has been developed for the synthesis of novel trifluoromethyl-containing piperidine and azepane β-amino ester stereoisomers. The synthesis started from readily available unsaturated bicyclic β-lactams and was based on oxidative cleavage of the ring C C double bond followed by ring closure of the diformyl intermediates in the presence of 2,2,2-trifluoroethylamine hydrochloride through reductive amination. The synthetic procedure has efficiently been extended towards the synthesis of mono- and difluorinated analogs.