Asymmetric Synthesis of Griffipavixanthone Employing a Chiral Phosphoric Acid-Catalyzed Cycloaddition.
Michael J SmithKyle D ReichlRandolph A EscobarThomas J HeaveyDavid F CokerScott E SchausJohn A PorcoPublished in: Journal of the American Chemical Society (2018)
Asymmetric synthesis of the biologically active xanthone dimer griffipavixanthone is reported along with its absolute stereochemistry determination. Synthesis of the natural product is accomplished via dimerization of a p-quinone methide using a chiral phosphoric acid 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, were performed in order to probe the mode of asymmetric induction.