Enantioselective Construction of Quinoxaline-Based Heterobiaryls and P,N-Ligands via Chirality Transfer Strategy

• DOI: 10.1021/acs.orglett.0c03827
• Publication Date: 2021-02-06T15:35:46Z
• Authors: Zeng Gao; Fang Wang; Jinlong Qian; Huameng Yang; Chungu Xia; Jinlong Zhang; Gaoxi Jiang
• Keywords: Chemical Sciences not elsewhere classified; chiral heteroaromatic biaryl backbones; Immunology; CuBr-catalyzed alkyne conjugate add.; MnO 2; Biochemistry; Microbiology; 01 natural sciences; Sociology; Environmental Sciences not elsewhere classified; Quinoxalinap; Genetics; Molecular Biology; dehydrogenative oxidation; bond oxidation; Computational Biology; Enantioselective Construction; ee; 0104 chemical sciences; Quinoxaline-Based Heterobiaryls; gram scale; Chirality Transfer Strategy Central.; precursor enantiomer; chirality control process; Biotechnology; Biological Sciences not elsewhere classified

Central-to-axial chirality transfer via C-N single bond oxidation was first achieved as a versatile and conceptually distinct strategy to prepare a new family of axially chiral heteroaromatic biaryl backbones and P,N-ligands (named as Quinoxalinaps) in gram scale. Two atropisomers of Quinoxalinaps (ee >99%) were readily accessed from the same precursor enantiomer by a simple dehydrogenative oxidation with MnO2 and t-BuOOH under mild conditions. Phosphine could be introduced into the ligands before or after the chirality control process. Moreover, these Quinoxalinap P,N-ligands performed well for both asymmetric reactions of the CuBr-catalyzed alkyne conjugate addition with up to -94% ee and AgOAc-catalyzed glycinate imine [3 + 2] annulation with 90% ee, respectively.