Continuous-Flow Synthesis of Δ9-Tetrahydrocannabinol and Δ8-Tetrahydrocannabinol from Cannabidiol

J Org Chem. 2023 May 5;88(9):6227-6231. doi: 10.1021/acs.joc.3c00300. Epub 2023 Apr 4.

Abstract

A challenging step in the preparation of tetrahydrocannabinol analogs is an acid-catalyzed intramolecular cyclization of the cannabidiol precursor. This step typically affords a mixture of products, which requires extensive purification to obtain any pure products. We report the development of two continuous-flow protocols for the preparation of (-)-trans9-tetrahydrocannabinol and (-)-trans8-tetrahydrocannabinol.