武汉大学董秀琴JACS:手性磷酸催化的去对称化策略实现阻转异构选择性(3+3)环化反应合成含远程1,4-双手性轴阻转异构体
The synthesis of atropisomeric biaryls has emerged as a significant frontier in organic chemistry. While notable advances have been achieved in the synthesis of atropisomers with a single chiral axis, the catalytic stereoselective assembly of atropisomers bearing multiple chiral axes remains a formidable challenge. Herein, we report a chiral phosphoric acid (CPA)-catalyzed atroposelective (3 + 3)-annulation between readily accessible propargylic alcohols and symmetric biaryltriols through a desymmetrization strategy, preparing a diverse array of distal 1,4-diaxial atropisomers possessing functionalized 2H-chromen and biaryldiol fragments. Notably, the protocol enables the divergent synthesis of two new sets of stereoisomers of distal 4,8-binaphthalen-1-yl-2H-chromenediols (BINCOLs) from identical symmetric triol precursors. The 1,4-diaxial BINCOLs demonstrate considerable utility as promising ligands in asymmetric catalysis, as evidenced by the successful application in Cu-catalyzed enantioselective C−H thiolation of ferrocene carboxamide. Furthermore, the 1,4-diaxial BINCOLs exhibit an aggregation-induced emission effect, highlighting their potential as a new class of polycyclic aromatic AIEgens.图4. 2-(2-羟基萘-1-基)苯-1,3-二醇底物范围 (图片来源于JACS)图6. 放大反应、合成转化反应及(S,R)-3a可应用于不对称催化转化反应中的手性配体 (图片来源于JACS)图8. 化合物3a的荧光放射波谱等 (图片来源于JACS)In summary, a CPA-catalyzed highly atroposelective (3 + 3) annulation reaction has been successfully established via a desymmetrization strategy, employing readily accessible propargylic alcohols and symmetric biaryltriols as the substrates. This protocol furnishes efficient and straightforward access to a diverse library of distal 1,4-diaxial atropisomers, which integrate functionalized 2H-chromene and biaryldiol motifs as key structural features. Notably, it enables the divergent synthesis of two stereoisomeric sets of distal 1,4-diaxial BINCOL derivatives. The utility of this chiral scaffold has been validated in asymmetric catalysis, where it serves as an effective chiral ligand in the Cu-catalyzed enantioselective C−H thiolation of ferrocene carboxamide. Furthermore, these polycyclic aromatic derivatives exhibit distinct AIE properties, highlighting their potential as a new class of AIE-active materials. The BINCOL skeleton thus represents a versatile and promising chiral scaffold with dual functionality in asymmetric synthesis and photophysical applications.DOI: https://doi.org/10.1021/jacs.6c04832
