Synthesis of CBD and Its Derivatives Bearing Various C4'-Side Chains with a Late-Stage Diversification Method.

A novel synthetic route for making (-)-CBD and its derivatives bearing various C4'-side chains is developed by a late-stage diversification method. Starting from commercially available phloroglucinol, the key intermediate (-)-CBD-2OPiv-OTf is efficiently and regioselectively prepared and further undergoes Negishi cross-coupling to furnish (-)-CBD. This approach allowed an efficient synthesis of (-)-CBD in a five-step total 52% yield on a 10 g scale. Furthermore, diversification on the C4'-side chain with this method can be realized in a wide range.