One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo- and heterogeneous Lewis acids

Victor R. L. J. Bloemendal, Bram Spierenburg, Thomas J. Boltje, Jan C. M. van Hest & Floris P. J. T. Rutjes

Published: 2021


Continuous flow chemistry holds great potential for the production of biologically relevant molecules. Herein, we present an approach for the continuous synthesis of cannabidiol and tetrahydrocannabinol in a one-flow system. The designed route consists of a reaction cascade involving Friedel-Crafts alkylation, subsequent ring opening and cyclisation in up to 45% yield. The reactions were successfully performed using both hetero- and homogeneous Lewis acids in continuous flow and provide yields that are similar to comparable batch processes.

Graphical abstract

A one-flow approach to CBD, (−)-trans8– and Δ9-THC is disclosed. The natural products were synthesised using homo- or heterogeneous Lewis acids.

Full Access Link: Journal of Flow Chemistry