Asymmetric Synthesis of Griffipavixanthone Employing a Chiral Phosphoric Acid-Catalyzed Cycloaddition

Asymmetric synthesis of the biologically active xanthone dimer griffipavixanthone (GPX) is reported along with its absolute stereochemistry determination. Synthesis of the natural product is accomplished <i>via</i> dimerization of a <i>p-</i>quinone methide (<i>p-</i>QM) using a chiral phosphoric acid (CPA) catalyst to afford a protected precursor in excellent diastereo- and enantioselectivity. Mechanistic studies, including an unbiased computational investigation of chiral ion-pairs using parallel tempering (PT), were performed in order to probe the mode of asymmetric induction