Brønsted Acid Catalyzed Asymmetric Synthesis of cis‐Tetrahydrocannabinoids

We report herein the catalytic asymmetric cyclization of 1‐aryl terpenols to afford enantiomerically highly enriched Δ9‐cis‐tetrahydrocannabinoid scaffolds in a single step. As powerful chiral catalysts strongly acidic imidodiphosphorimidates (IDPis) have been identified which furnish the products with good yields and excellent enantioselectivity. Upon MOM‐deprotection some naturally occurring cannabimimetica such as (−)‐cis‐Δ9‐tetrahydrocannabinol and (−)‐perrottetinene as well as some unnatural analogues were made accessible along a merely 3‐step biomimetic sequence (MOM=methoxymethyl). An asymmetric Brønsted acid catalyzed and biomimetic cyclization of 1‐aryl terpenols as a platform strategy for the synthesis of Δ9‐cis‐tetrahydrocannabinoids is described. This synthesis features the most direct synthetic access to this product class and requires only 3 steps from readily available precursors with exceptionally low catalyst loadings of as low as 0.5 mol % (MOM=methoxymethyl, IDPi=imidodiphosphorimidates).