Scalable Cu(Ii)-Mediated Intramolecular Dehydrogenative Phenol-Phenol Coupling: Concise Synthesis Of Enantiopure Axially Chiral Homo- And Hetero-Diphenols

An intramolecular dehydrogenative homo- and hetero-coupling of phenols has been successfully developed for quick preparation of enantiopure axial diphenols under mild Cu(II)-mediated conditions, using ((4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanol as the chiral auxiliary. The commercially available (R)-alpha-methylbenzylamine was identified as the best amine ligand for Cu(II) in the reactions. A variety of homo/hetero bis-dihydroxylbenzoate substrates were examined, affording the corresponding axially chiral diphenols with satisfactory to excellent diastereomeric ratios, and a representative scalable preparation was also attempted. A formal synthesis of natural product (+)-deoxyschizandrin has been achieved in this work using one axially chiral diphenol as the synthetic intermediate. (C) 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.