Deaminative Thiocyanation and Halogenation of Aliphatic Amines

Comprehensive Summary The deaminative functionalization of aliphatic amines via diazonium salts has potential synthetic value but remains challenging in modern synthetic chemistry. Aliphatic primary amines are ubiquitous building blocks in natural products and bioactive molecules, however, the high C(sp 3 )–N bond dissociation energy restricts their direct transformation. Herein, we report a practical method for the deaminative thiocyanation and halogenation of aliphatic primary amines using inexpensive nitrate salts as the NO₂ source. Readily available NH₄SCN plays a dual role as both reductant and thiocyanating reagent. Unlike traditional diazotization protocols that require isolation and accumulation of unstable diazonium species, the generation of transient diazonium salts render this process safer and more controllable. This protocol exhibits a broad substrate scope, mild reaction conditions, easy scalability, and can be applied to the late‐stage functionalization of drug derivatives. Mechanistic studies reveal that NO₂ is generated via reduction of nitrate by NH 4 SCN under acidic conditions, and a phenonium intermediate is possibly involved for phenethylamine‐type substrates. Moreover, this strategy can be extended to deaminative chlorination and bromination in the presence of the corresponding halide salts, further expanding its synthetic applications.