Enantioselective Synthesis of Planar‐Chiral Macrocycles through Asymmetric Electrophilic Aromatic Amination

• Published in: Angewandte Chemie International Edition Vol. 61; no. 22; pp. e202201064 - n/a
• Main Authors: Wang, Donglei, Shao, Ying‐Bo, Chen, Yunrong, Xue, Xiao‐Song, Yang, Xiaoyu
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 23.05.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Amination; Asymmetric Catalysis; Asymmetric synthesis; Asymmetry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Enantiomers; Functional groups; Macrocycles; Organocatalysis; Paracyclophanes; Phosphoric acid; Physical Sciences; Science & Technology; Synthesis; BRONSTED ACID; TRANSFORMATION; Asymmetric Catalysis; Amination; Paracyclophanes; Macrocycles; Organocatalysis
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202201064

An efficient approach for asymmetric synthesis of planar‐chiral macrocycles (paracyclophanes) has been disclosed through enantioselective electrophilic aromatic aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. A wide range of chiral macrocycles bearing varied ring sizes (16 to 23‐membered) and functional group‐containing ansa chains were readily afforded using this method, with excellent yields and high enantioselectivities (23 examples, up to 99.5 : 0.5 er). Experimental studies and DFT calculations were performed to elucidate the mechanism and origin of stereoselectivities of these reactions. Preliminary utilization of the planar‐chiral macrocycle as chiral organocatalyst showcased the potential applications of these novel chiral skeletons. An efficient method for asymmetric synthesis of planar‐chiral macrocycles has been developed through enantioselective electrophilic aromatic aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. A wide array of planar‐chiral macrocycles bearing ansa chains with varied length (12‐member to 19‐member) and various functional groups were generated using this method with high to excellent enantioselectivities.