Synthesis and Reactions of a Stable o-Quinoid 10-π-Electron System, Furo[3,4-c]pyridine

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Abstract
Methyl 4,6-dichloro-3-(diethylamino)furo[3,4-c]pyridine-1-carboxylate (6), an intermediate in the Hamaguchi−Ibata reaction involving the RhII-catalyzed intramolecular reaction of a diazo group with the carbonyl of an adjacent amido group, has been isolated and characterized. PM3 calculations reveal the heat of formation (ΔHf) of this remarkably stable molecule to be −77.7 kcal/mol. Compound 6 undergoes a facile Diels−Alder cycloaddition with a variety of dienophiles to give polysubstituted isoquinoline derivatives via ring opening of initially formed cycloadducts. In each case the cycloaddition proceeds with high regioselectivity, with the electron-withdrawing group located ortho to the amino group. The most favorable FMO interaction is between the HOMO of the azaisobenzofuran 6 and the LUMO of the dienophile. The atomic coefficient at the ester carbon of the azaisobenzofuran 6 is larger than the amino center, and this nicely accommodates the observed regioselectivity.