Scalable Cu(II)-mediated intramolecular dehydrogenative phenol-phenol coupling: Concise synthesis of enantiopure axially chiral homo- and hetero-diphenols

• Published in: Chinese chemical letters 2021-01, Vol.32 (1), p.380-384
• Main Authors: Gu, Yuefei, Wang, Tianyang, Gao, Ming, Yao, Zhu-Jun
• Format: Article
• Language: English
• Subjects: Axially chirality; Chiral auxiliary; Cu(II)-mediated oxidation; Dehydrogenative phenol-phenol coupling; Diastereoselectivity
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2020.02.015

A series of intramolecular homo/hetero phenol-pheno couplings have been achieved with Cu(II)-mediated oxidative conditions, delivering the corresponding enantiopure axially chiral diphenols. [Display omitted] 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)-α-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.