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).

Stereoselective Synthesis of Chiral α-SCF3-β-Ketoesters Featuring a Quaternary Stereocenter / M.F. Boselli, C. Faverio, E. Massolo, L. Raimondi, A. Puglisi, M. Benaglia. - In: SYMMETRY. - ISSN 2073-8994. - 13:1(2021), pp. 92.1-92.16.

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

M.F. Boselli;C. Faverio;E. Massolo;L. Raimondi;A. Puglisi;M. Benaglia
Ultimo
2021

Abstract

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).
asymmetric synthesis; fluorinated compounds; chiral auxiliary; stereoselectivity; trifluoromethylthio-substituted ketones
Settore CHIM/06 - Chimica Organica
Raising up Catalysis for Innovative Developments (SURSUMCAT)
Enabling TECHNOlogies-driven chemistry: a tailored TRAINing research program for batch and flow synthesis of chiral amino derivatives (TECHNOTRAIN)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/813899
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