An Ugi-intramolecular Diels-Alder route to highly substituted tetrahydroepoxyisoindole carboxamides

The four component Ugi reaction of 2-furaldehyde, an alkenoic acid (three examples), an isonitrile (eight examples) and an amine (eight examples) affords rapid access to a family of acetylenic furan analogues, which on heating undergo an intramolecular Diels-Alder (IMDA) reaction yielding highly substituted tricyclic lactams (17 examples) in good to excellent yields (38-72% two-steps). This Ugi-IMDA reaction proved to be highly substituent tolerant across both the isonitriles and amines examined. In one instance, with N,N- dimethylaminopropylamine, a second equivalent of alkynoic acid was required to afford a good yield of the desired tricyclic lactam.