Pd-Catalyzed C-H Lactonization for Expedient Synthesis of Biaryl Lactones and Total Synthesis of Cannabinol

A practical Pd(II)/Pd(IV)-catalyzed carboxyl-directed C-H activation/C-O cyclization to construct biaryl lactones has been developed. The synthetic utility of this new reaction was demonstrated in an atom-economical and operationally convenient total synthesis of the natural product cannabinol from commercially available starting materials, with the newly developed method used for two key steps.