The Diels-Alder Approach towards Cannabinoid Derivatives and Formal Synthesis of Tetrahydrocannabinol (THC)

Based on the Diels-Alder reaction of vinylchromenes with electron-poor dienophiles, we developed a strategy for the synthesis of tetrahydrocannabinol derivatives. Substituted vinyl chromenes could be converted with several dienophiles to successfully isolate several complex molecules. These molecules already contain the cannabinoid-like base structure and further processing of one such derivative led to a precursor of Δ${}^9$-tetrahydrocannabinol. The most challenging step towards this precursor was an epoxidation step that was ultimately achieved via dimethyl dioxirane.