Collect. Czech. Chem. Commun. 2001, 66, 1257-1268

Tetrahydrocannabinol Revisited: Synthetic Approaches Utilizing Molybdenum Catalysts

Andrei V. Malkov* and Pavel Kočovský*

Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, U.K.


9-Tetrahydrocannabinol 1 and its isomers were synthesized via domino-type methodology. The first approach, leading to (±)-1, relies on the Mo(IV)-catalyzed, one-pot cascade reaction of citral (4) with olivetol (15), affording (±)-∆9-tetrahydrocannabinol as a 69 : 31 mixture of the trans- (natural) and cis-isomers in 20% yield. The alternative approach, leading to natural (-)-1, commenced with epoxidation of (+)-limonene (R)-(+)-16; opening of the resulting cis-epoxide 17 with PhSeNa, followed by elimination, afforded tertiary alcohol 21, whose acetate 22 was treated with olivetol 15 in the presence of Mo(II) catalyst IV to afford (-)-1 in 52% yield.

Keywords: Terpenoids; Cannabinoids; Total synthesis; Asymmetric catalysis; Allylic substitution; Cascade reactions; Natural products.

References: 31 live references.