近日，国科大杭州高等研究院张夏衡团队研究了N-硝基胺的直接脱胺功能化。这一研究成果发表在2025年10月27日出版的《自然》杂志上。

胺类是生物活性分子中最常见的官能团之一。然而，传统芳胺转化方法主要依赖重氮盐中间体，这类盐类化合物因易爆特性存在显著安全风险。

研究组提出一种通过形成N-硝胺的直接脱氨策略，可将惰性芳基碳氮键直接转化为多种官能团（包括碳-卤键、碳-杂原子键及碳-碳键）。该操作简便的通用方案通过将脱氨官能团化与过渡金属催化芳基化反应相结合，建立了一锅法脱氨交叉偶联的统一策略，从而简化了合成过程及后期官能团化步骤。

相较于其他脱氨官能团化方法，该转化的核心优势在于其普适性——适用于几乎所有药用相关杂芳胺类别，以及不同电子效应和立体结构的苯胺衍生物，且不受氨基取代位点影响。结合实验观测与理论分析的机理研究表明，该脱氨过程中N-硝胺主要呈现芳基正离子等效反应活性。这项研究揭示了直接脱氨策略在合成化学中的重要潜力，为传统易爆危险的芳基重氮盐化学提供了更安全的替代路径。

附：英文原文

Title: Direct deaminative functionalization with N-nitroamines

Author: Tu, Guangliang, Xiao, Ke, Chen, Xiaoping, Xu, Haoran, Zeng, Haifeng, Zhang, Fangjiang, Xue, Xiaosong, Zhang, Xiaheng

Issue&Volume: 2025-10-27

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 salts3,4. Here, we report a direct deaminative strategy through the formation of N-nitroamines, allowing the direct conversion of inert aromatic CN bonds into an array of other functional groups, CX (CBr, CCl, CI, CF, CN, CS, CSe, CO) and CC 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.

DOI: 10.1038/s41586-025-09791-5

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