One-Pot Total Synthesis of Cannabinol via Iodine-Mediated Deconstructive Annulation

The thermal degradation of cannabichromene (CBC, 3) is dominated by cationic reactions and not by the pericyclic rearrangements observed in model compounds. The rationalization of these differences inspired the development of a process that coupled, in an aromatization-driven single operational step, the condensation of citral and alkylresorciniols to homoprenylchromenes and their in situ deconstructive annulation to benzo[c]chromenes. This process was applied to a total synthesis of cannabinol (CBN, 5) and to its molecular editing.