Asymmetric Aminocatalysis Applied to the Synthesis of Structures Inspired by Δ8-Tetrahydrocannabinoids

The development and optimization of synthetic routes to bicyclic and tricyclic benzofuzed heterocycles have become increasingly relevant due to the biological properties of these structures and the rigid nature of such molecules. Δ⁸-THC, a member of the cannabinoid family with potential for the treatment of neurological disorders, contains a tetrahydro-6H-benzo[c]chromene framework. Therefore, the aim of this work is to carry out the asymmetric aminocatalysis of Δ⁸-THC-inspired structures through the enantioselective Diels–Alder reaction using MacMillan catalysts. Using 30 mol% of the organocatalyst, the Diels–Alder adduct was obtained in 46% yield with a diastereomeric ratio >95:5. Subsequently, following reduction, the chroman was obtained in 22% yield through an intramolecular cyclization via the copper-catalyzed etherification of aryl bromides, promoted by visible light (460 nm) through an energy transfer mechanism.