Direct deaminative functionalization with N-nitroamines

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Abstract

Amines are among the most common functional groups in bioactive molecules¹. Despite this prevalence, conventional means of converting aromatic amines rely heavily on diazonium intermediates², which pose significant safety risks due to the explosive nature of these salts^3,4. Here, we report a direct deaminative strategy through the formation of N-nitroamines, allowing the direct conversion of inert aromatic C−N bonds into an array of other functional groups, C−X (C−Br, C−Cl, C−I, C−F, C−N, C−S, C−Se, C−O) and C−C bonds. This operationally simple, general protocol establishes a unified strategy for one-pot deaminative cross-couplings by integrating deaminative functionalization with transition-metal-catalyzed arylation, thereby streamlining synthesis and late-stage functionalization. The key advantages of this transformation over other deaminative functionalization methods lies in its versatility across nearly all classes of medicinally relevant heteroaromatic amines, as well as electronically and structurally diverse aniline derivatives, regardless of the position of the amino group. Mechanistic studies, supported by both experimental observations and theoretical analysis, suggest that the aryl cation equivalent reactivity of N-nitroamines is generally favoured in this deaminative process. This study highlights the significant potential of the direct deamination approach in synthetic chemistry, offering a safer alternative to the traditionally explosive and hazardous aryldiazonium chemistry.

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