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

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, (−)- trans -Δ 8 - and Δ 9 -THC is disclosed. The natural products were synthesised using homo- or heterogeneous Lewis acids.