Atroposelective synthesis of biaxial bridged eight-membered terphenyls via a Co/SPDO-catalyzed aerobic oxidative coupling/desymmetrization of phenols

• Published in: Nature communications Vol. 15; no. 1; pp. 4591 - 7
• Main Authors: Wang, Shuang-Hu, Wei, Shi-Qiang, Zhang, Ye, Zhang, Xiao-Ming, Zhang, Shu-Yu, Dai, Kun-Long, Tu, Yong-Qiang, Lu, Ka, Ding, Tong-Mei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 140/146; 140/58; 639/638/403/933; 639/638/77/883; 639/638/77/888; Aromatic compounds; Bridge construction; Chirality; Enantiomers; Humanities and Social Sciences; multidisciplinary; Phenols; Pyrrolidine; Science; Science (multidisciplinary); Synthesis; Terphenyls
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48858-1

Bridged chiral biaryls are axially chiral compounds with a medium-sized ring connecting the two arenes. Compared with plentiful methods for the enantioselective synthesis of biaryl compounds, synthetic approaches for this subclass of bridged atropisomers are limited. Here we show an atroposelective synthesis of 1,3-diaxial bridged eight-membered terphenyl atropisomers through an Co/SPDO (spirocyclic pyrrolidine oxazoline)-catalyzed aerobic oxidative coupling/desymmetrization reaction of prochiral phenols. This catalytic desymmetric process is enabled by combination of an earth-abundant Co(OAc) 2 and a unique SPDO ligand in the presence of DABCO (1,4-diaza[2.2.2]bicyclooctane). An array of diaxial bridged terphenyls embedded in an azocane can be accessed in high yields (up to 99%) with excellent enantio- (>99% ee) and diastereoselectivities (>20:1 dr). Biaryl compounds with an axial chirality are valuable architectures but few methods have been developed for the construction of bridged biaryls, a subclass of these compounds that bear a tether to connect the two arenes and form a medium-sized ring. Here, the authors design a Co/SPDO-catalyzed aerobic oxidative coupling/desymmetrization sequence of prochiral phenols for the enantioselective synthesis of biaxial bridged m-terphenyls embedded in an azocane.