Copper(II)-Amine Complex-Mediated Intramolecular Coupling of Gallates: A Bioinspired Solution to the Atroposelective Synthesis of Ellagitannins

Total syntheses of the C-glucosidic ellagitannins (-)-punicacortein A, (-)-epipunicacortein A and (+)-castalin were accomplished for the first time, and those of the glucopyranosic ellagitannins (+)-tellimagrandin I and (+)-pedunculagin were revisited. The atroposelective construction of their characteristic hexahydroxydiphenoyl (HHDP) and nonahydroxyterphenoyl (NHTP) units relied on the use of different cupric-amine complexes under different reaction conditions to mediate the intramolecular dehydrogenative coupling of galloyl groups at different positions of glucose cores. In particular, the monodentate n-butylamine and the bidentate (-)-sparteine were found to be complementary in their capacity to promote the regio- and atroposelective coupling of galloyl groups on a 4C1-glucopyranosic core into 2,3-O-(S)- and/or 4,6-O-(S)-HHDP units. Furthermore, replacing (-)-sparteine by its optical antipode not only counteracted the substrate-controlled induction of atroposelectivity to forge a 4,6-O-(R)-HHDP unit, but it also enabled a 4C1 to 1C4 ring flip of the glucopyranosic core and hence the formation of 2,4-O-(R)- and 3,6-O-(R)-HHDP units, such as those featured in the glucopyranosic ellagitannins phyllanemblinin B and geraniin.