A one-pot, three-component synthesis of polysubstituted furo[2,3-c] quinoline 1 was developed based on the new reactivity profile of alpha-(4-nitrophenyl)-alpha-isocyanoacetates. Simply mixing aldehydes 2, ortho-alkynylanilines 3, and alpha-(4-nitrophenyl)-alpha-isocyanoacetates 4 in methanol at room temperature, followed by addition of toluene and heating to reflux, provided the polysubstituted furo[2,3-c] quinolines in moderate to excellent yields. Mechanistically, the three-component reaction of 2, 3, and 4 leading to 5-alkoxyoxazoles was followed by a domino sequence involving Diels-Alder/retroDiels-Alder/oxidation reactions. In this one-pot process, five chemical bonds were created with concurrent formation of two heterocyclic rings. The reaction was performed under thermal conditions and no external reagent was needed to promote this mechanistically intriguing reaction.