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

Abstract

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.