Asymmetric Synthesis of (-)-Cannabidiol (CBD), (-)-Δ 9 -Tetrahydrocannabinol (Δ 9 -THC) and Their cis Analogs Using an Enantioselective Organocatalyzed Diels-Alder Reaction.

Herein we describe an asymmetric synthesis of the pharmacologically relevant natural (-)- trans -CBD and psychoactive (-)- trans -Δ 9 -THC, as well as their synthetic cis diastereomers. The key step is an enantioselective Diels-Alder reaction catalyzed by a prolinol-based catalyst, which provides the cyclohexene carbaldehyde intermediate in good yield and high enantiomeric excess. Optimization of the substituted resorcinol protecting groups to avoid harsh and low-yield deprotection of the acid sensitive resorcinol moiety is also described.