Stereoselective Synthesis of Chiral α-SCF3-β-Ketoesters Featuring a Quaternary Stereocenter

Symmetry

Chiara Faverio¹  Laura Raimondi¹  Alessandra Puglisi¹  Maurizio Benaglia¹  MonicaFiorenza Boselli¹  Elisabetta Massolo¹ 

[1] Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, I-20133 Milano, Italy;

关键词: asymmetric synthesis;    fluorinated compounds;    chiral auxiliary;    stereoselectivity;    trifluoromethylthio-substituted ketones;   

DOI  :  10.3390/sym13010092

来源: DOAJ

【 摘 要 】

The development of new and efficient methods, reagents, and catalysts for the introduction of fluorine atoms or fluorinated moieties in molecular scaffolds has become a topic of paramount importance in organic synthesis. In this framework, the incorporation of the SCF₃ group into organic molecule has often led to beneficial effects on the drug’s metabolic stability and bioavailability. Here we report our studies aimed to the stereoselective synthesis of chiral α-SCF₃-β−ketoesters featuring a tetrasubstituted stereocenter. The use of a chiral auxiliary was crucial to synthesize enantiopure enamines that were reacted with N-trifluoromethylthio saccharin or phthalimide, to afford enantioenriched α-SCF₃-tetrasubstitued β-keto esters. By using a readily available, inexpensive chiral diamine, such as trans-1,2-diaminocyclohexane, the fluorinated products could be obtained in modest to good yields, and, after the removal of the chiral auxiliary, α-substituted- α trifluoromethylthio-β−ketoesters were isolated with high enantioselectivity (up to 91% ee).

【 授权许可】

Unknown