The Diels-Alder Approach towards Cannabinoids

Abstract

Starting from the efficient synthesis of benzopyrans by base-catalyzed condensation reactions between substituted 2-hydroxybenzaldehydes and α,β-unsaturated aldehydes, thermal, Lewis acid catalyzed and enantioselective organo-promoted Diels-Alder reactions towards the tricyclic cannabinoid system are presented. The procedures are exemplified by the synthesis of a pentacycle and various tricycles respectively, in up to 95% enantiomeric excess and provide a versatile entry to this group of natural products with tetrahydrocannabinol (THC) being the most prominent one. Most published strategies are based on the formation of the tricyclic system by condensation between readily available phenols and monoterpenes, whereas we present a novel approach to cannabinoid derivatives based on a modular synthesis.

natural product synthesis - cannabinoids - asymmetric synthesis

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Crystallographic data (excluding structure factors) for the structures reported in this work have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-258378 (7a) and CCDC-258379 (14), respectively. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge, UK.