Atroposelective Synthesis of Biaryl N‐Oxides via Cu‐Catalyzed De Novo Heteroaromatic N‐Oxide Ring Formation

• DOI: 10.1002/advs.202405743
• Publication Date: 2024-08-09T12:27:10Z
• Authors: Ke Ma; Ting Qi; Lei Hu; Chen Chen; Wan Wang; Jun‐Long Li; Cheng Peng; Gu Zhan; Bo Han
• Keywords: Base (topology)

Abstract Heteroaromatic N ‐oxides, renowned for their highly polar N─O bond and robust structure, exhibit significant bioactivities have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts ligands organic synthesis. Despite importance, synthesizing these compounds is challenging, necessitating starting materials or resolution processes. Catalytic strategies rely on functionalization ‐oxide compounds, leading to products with relatively limited skeletal diversity. This study introduces Cu‐catalyzed atroposelective method ‐oxides via de novo ring formation. mild efficient approach achieves excellent stereoselectivities (up 99:1 er), enabling production wide array novel scaffolds. The product 3f demonstrates high stereoselectivity recyclability catalyst. Additionally, 3e exhibits promising therapeutic efficacy against triple‐negative breast cancer, IC 50 values 4.8 5.2 µ m MDA‐MB‐231 MDA‐MB‐468 cells, respectively. research not only advances synthesis challenging but also encourages further exploration entities bioactive small molecules.