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

Abstract

Abstract 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 Δ9‐tetrahydrocannabinol. The most challenging step towards this precursor was an epoxidation step that was ultimately achieved via dimethyl dioxirane.

Keywords

• natural products
• medicinal chemistry
• fused-ring systems
• cycloaddition reactions
• Diels-Alder reactions