Bis(trimethylsilyl)ketene acetals as C,O-dinucleophiles: One-pot formation of polycyclic γ- and δ-lactones from pyridines and pyrazines

Article abstract of DOI:10.1002/ejoc.200500162

Bis(trimethylsilyl)ketene acetals react with pyridines, quinoline and isoquinoline in the presence of stoichiometric amounts of methyl chloroformate to give the corresponding dihydropyridine-, dihydroquinoline- and dihydroisoquinoline-substituted carboxylic acids in satisfactory yields. The regio- and diastereoselectivities of the addition reactions, together with the presence or absence of rotamers, have been established. The isolated acids react with peracids to give β-hydroxy-δ-lactones through an intramolecular reaction. Similar lactonizations could also be brought about directly from the azaaromatic compounds in one-pot reactions with silica gel, iodine or bromine. In these cases δ-lactones or β-halo-δ-lactones were produced. The behaviour of pyrazines in these transformations is peculiar, since methyl chloroformate on its own induces the formation, through interaction with both nitrogen atoms, of polycyclic γ-lactones, a reaction formally reminiscent of the double nucleophilic addition of the same ketene acetals to (arene)tricarbonylchromium complexes. Most of the new structures were assigned through X-ray crystal structure determinations. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.