https://www.nature.com/articles/s41586-025-09791-5

https://www.cas.cn/syky/202510/t20251030_5086701.shtml

A research team at the CAS University of Advanced Sciences in Hangzhou has found a direct activation pathway for aromatic amines. They used the in-situ formation of N-nitramine intermediates from aromatic amines mediated by nitric acid, followed by the removal of nitrous oxide to achieve efficient and direct conversion of aromatic C-N bonds to various C-X and C-C bonds. Compared to the classic Sandmeyer reaction conditions for aromatic amine conversion, the new method demonstrates advantages in polynitrogenous heterocyclic systems commonly used in drug synthesis. Compared to other deamination functionalization methods, this strategy’s advantage lies in its excellent versatility, utilizing only simple, readily available laboratory reagents. It is applicable to almost all types of pharmaceutical heteroaromatic amines and aniline derivatives with varying electronegativity and structures, unrestricted by amino positions, and capable of kilogram-scale production with simple operation.

They further developed a one-pot deamination cross-coupling strategy. By simply adding the appropriate coupling reagent directly to the deamination reaction intermediate, various cross-coupling reactions can be completed in the same reaction system, such as Negishi coupling, reductive cross-coupling, Ullmann-Ma reaction, Buchwald-Hartwig reaction, metal photoredox catalysis, Hirao reaction, and sulfonation. This opens up new avenues for the rapid construction of complex molecules from readily available raw materials.