Straightforward access to tetrahydropyridine and piperidine-fused fluorolactones from pyridines and bis(trimethylsilyl)ketene acetals

The interaction of bis(trimethylsilyl)ketene acetals with various pyridines provides a direct, general, diastereoselective access to fluorolactones via the formation of dihydropyridine-substituted carboxylic acids. These in turn reacted with selectfluor as the source of electrophilic fluorine. Whereas a discrimination of the double bonds devoid of fluorine and those bearing fluorine was observed in the case of electrophiles such as iodine, bromine and peracids, no such differentiation took place in the case of selectfluor since, besides 3,5-difluorolactones, the formation of gem-difluorolactones also took place. Moreover, the formation of two stereoisomeric fluorolactones during the lactonization of tetrahydropyridine-substituted carboxylic acids, obtained upon the interaction of (trimethylsilyl)ketene acetals with the previous lactones, could be ascribed to conformational modifications. In all the cases examined a trans, diaxial addition of the electrophile and of the carboxylate is observed. The stereochemical outcome of these reactions was assessed both by NMR spectroscopy and by X-ray crystallography.