Asymmetric synthesis of trifluoromethyl-piperidine based γ-amino acids and of trifluoromethyl-indolizidines

The asymmetric synthesis of trifluoromethyl-piperidine-based γ-aminoacids and of indolizidines bearing a trifluoromethyl group is reported. These rarely described compounds are prepared in a highly enantio-enriched form employing as key step an intramolecular Mannich type process, involving an enantiopure Tfm-aminoketal and ethyl oxobutenoate as aldehyde partner. Used strategy together with obtained compounds allows the access to a wide range of Tfm-N-(poly)heterocycles, structures of obvious interest for the research of new bioactive drugs.

Graphical abstractHighly enantio-enriched Tfm-piperidines based γ-aminoacids and Tfm-indolizidines, rarely described compounds, are prepared efficiently using an intramolecular Mannich-type strategy.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► An efficient pathway to highly enantio-enriched trifluoromethyl-piperidines is fully described. ► The first synthesis of an enantio-enriched Tfm-piperidine based γ-aminoacid is reported. ► A facile and concise access to enantio-enriched Tfm-indolizidines is proposed.