Sirisuk Keereewan, Chutima Kuhakarn, Pawaret Leowanawat, Saowanit Saithong, Vichai Reutrakul, Darunee Soorukram*

We successfully developed an efficient synthetic strategy to prepare enantioenriched gem-difluoromethylenated spiro-pyrrolidinyl and spiro-piperidinyl oxindoles. The reaction involved fluoride-mediated diastereoselective nucleophilic addition of PhSCF2SiMe3 to chiral N-tert-butanesulfinyl ketimines derived from isatins to install the quaternary chiral center at C-3 of the oxindole frameworks. The resulting adducts were further manipulated through the hydrolysis of the N-sulfinylimine and N-alkylation followed by reductive cleavage of the phenylsulfanyl group and radical cyclization leading to a series of chiral gem-difluoromethylenated spiro-pyrrolidinyl and spiropiperidinyl oxindoles, each as a single diastereomer after chromatographic purification. Synthetic transformations of the enantioenriched gem-difluoromethylenated spiropyrrolidinyl and spiro-piperidinyl oxindoles via reduction of the carbonyl moiety to give alcohol products as well as cyclization to give diaza-tetracyclic skeletons demonstrated the synthetic utility of the synthesized compounds of the present work which could have particular interest and significance in organic synthesis and pharmaceutical applications.