Synthesis and reactions of a stable o-quinoid 10-pi-electron system, furo[3,4-c]pyridine

Methyl 4,6-dichloro-3-(diethylamino)furo[3,4-c]pyridine-1-carboxylate (6), an intermediate in the Hamaguchi-Ibata reaction involving the Rh-II-catalyz ed intramolecular reaction of a diazo group with the carbonyl of an adjacen t amido group, has been isolated and characterized. PM3 calculations reveal the heat of formation (Delta H-f) of this remarkably stable molecule to be -77.7 kcal/mol. Compound 6 undergoes a facile Diels-Alder cycloaddition wi th a variety of dienophiles to give polysubstituted isoquinoline derivative s via ring opening of initially formed cycloadducts. In each case the cyclo addition 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 dienophi le. The atomic coefficient at the ester carbon of the azaisobenzofuran 6 is larger than the amino center, and this nicely accommodates the observed re gioselectivity.