Flow synthesis of annulated 5-aryl-substituted pyridines by tandem intramolecular inverse-electron-demand hetero-/retro-Diels-Alder reaction

5-Aryl-substituted annulated pyridines can be accessed directly from the corresponding acetylene substituted pyrimidines through an intramolecular inverse-electron-demand hetero-/retro-Diels-Alder (ihDA/rDA) reaction cascade carried out in continuous flow. Exploiting this new process, a series of cycloalka[c]pyridines that represent useful building blocks for medicinal chemistry were prepared in good to excellent yields with short processing times (<45 min). Importantly, utilizing the ability to superheat solvents in flow permits the replacement of typically employed high boiling solvents (e.g., nitrobenzene or chlorobenzene) with toluene.