The Diels–Alder Approach to Δ9‐Tetrahydrocannabinol Derivatives

Abstract

AbstractWe have developed an efficient strategy for the synthesis of tetrahydrocannabinol derivatives based on an unsubstituted aromatic compound. A Diels–Alder reaction of vinylchromene with an electron‐poor dienophile gave a tricycle. We describe several methods for the functionalization of this compound, e.g., alkylation, reduction, and lactonization. We also studied the hydrogenation of some of these functionalized cannabinoid compounds to give cannabinoid‐like skeletons. Of these reactions, a tetracycle containing a lactone gave the best result, with a quantitative yield using PtO2 (5 mol‐%) and an atmospheric pressure of hydrogen. These numerous reactions can be applied to substituted aromatic starting materials to obtain a facile and modular route to Δ9‐tetrahydrocannabinol, or alternatively, with different substituents, to other cannabinoid analogues.