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.