N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution

• Published in: Nature communications Vol. 15; no. 1; pp. 2338 - 11
• Main Authors: Li, Jiayan, Dong, Ziyang, Chen, Yang, Yang, Zhanhui, Yan, Xinen, Wang, Meng, Li, Chenyang, Zhao, Changgui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.03.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 140/131; 140/146; 140/58; 639/638/403/933; 639/638/77/883; 639/638/77/888; Aromatic compounds; Asymmetry; Carbenes; Catalysis; Chemical synthesis; Chemistry; Drug discovery; Enantiomers; Enzymes; Humanities and Social Sciences; Inclusion; multidisciplinary; Optimization; Science; Science (multidisciplinary); Solvents; Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46376-8

Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of planar-chiral cyclophanes. This transformation occurs through a dynamic kinetic resolution (DKR) process to convert racemic substrates into planar-chiral macrocycle scaffolds in good to high yields with high to excellent enantioselectivities. The ansa chain length and aromatic ring substituent size is crucial to achieve the DKR approach. Controlled experiments and DFT calculations were performed to clarify the DKR process. Planar-chiral cyclophanes are important for drug discovery but the enantioselective synthesis of planar-chiral cyclophanes remains challenging. Here the authors describe an N-heterocyclic carbene-catalyzed asymmetric construction of planar-chiral cyclophanes.