title: Symmetry in Cascade Chirality-Transfer Processes: A Catalytic Atroposelective Direct Arylation Approach to BINOL Derivatives.
abstract: Herein we disclose a scalable organocatalytic direct arylation approach for the regio- and atroposelective synthesis of non-C2-symmetric 2,2'-dihydroxy-1,1'-binaphthalenes (BINOLs). In the presence of catalytic amounts of axially chiral phosphoric acids, phenols and naphthols are coupled with iminoquinones via a cascade process that involves sequential aminal formation, sigmatropic rearrangement, and rearomatization to afford enantiomerically enriched BINOL derivatives in good to excellent yields. Our studies suggest that the (local) symmetry of the initially formed aminal intermediate has a dramatic impact on the level of enantioinduction in the final product. Aminals with a plane of symmetry give rise to BINOL derivatives with significantly lower enantiomeric excess than unsymmetrical ones featuring a stereogenic center. Presumably asymmetric induction in the sigmatropic rearrangement step is significantly more challenging than during aminal formation. Sigmatropic rearrangement of the enantiomerically enriched aminal and subsequent rearomatization transfers the central chirality into axial chirality with high fidelity.
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, P.R. China.
authors.forename: Jin-Zheng
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, P.R. China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Chemistry, Rice University, BioScience Research Collaborative , 6500 Main Street, Room 380, Houston, Texas 77030, United States.
authors.forename: László
authors.initials: L
authors.lastname: Kürti
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University , 24 Tongjia Xiang, Nanjing 210009, P.R. China.
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Xu
mesh_terms: D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D009284:Naphthols / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry; D010756:Phosphoric Acids / Q000737:chemistry; D011809:Quinones / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C406944:BINOL, naphthol; D009284:Naphthols; D010636:Phenols; D010756:Phosphoric Acids; D011809:Quinones; C116897:iminoquinone