Atroposelective Access to 1,3‐Oxazepine‐Containing Bridged Biaryls via Carbene‐Catalyzed Desymmetrization of Imines

• Published in: Angewandte Chemie International Edition 2023-01, Vol.62 (1), p.e202211977-n/a
• Main Authors: Yang, Xing, Wei, Liwen, Wu, Yuelin, Zhou, Liejin, Zhang, Xinglong, Chi, Yonggui Robin
• Format: Article
• Language: English
• Subjects: Aminophenol; Atropisomerism; Bridged Biaryls; Carbenes; Catalysts; Density functional theory; Enantiomers; Imines; Methane; Molecular orbitals; N-Heterocyclic Carbenes; Organocatalysis; Oxazepines; Oxidation; Substrates; Umpolung
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202211977

We disclose herein an atroposelective synthesis of novel bridged biaryls containing medium‐sized rings via N‐heterocyclic carbene organocatalysis. The reaction starts with addition of the carbene catalyst to the aminophenol‐derived aldimine substrate. Subsequent oxidation and intramolecular desymmetrization lead to the formation of 1,3‐oxazepine‐containing bridged biaryls in good yields and excellent enantioselectivities. These novel bridged biaryl products can be readily transformed into chiral phosphite ligands. Preliminary density function theory calculations suggest that the origin of enantioselectivity arises from the more favorable frontier molecular orbital interactions in the transition state leading to the major product. An atroposelective synthesis of novel bridged biaryls containing 1,3‐oxazepine medium‐sized rings is enabled by N‐heterocyclic carbene organocatalysis. Addition of the carbene catalyst to the aminophenol‐derived aldimine substrate followed by oxidation and intramolecular desymmetrization gave the desired bridged biaryls in good yields (up to 90 % yield) and excellent enantioselectivities (up to 99 % ee).