Advances in C—N₃ Retention Reactions Involving Organic Azides

Abstract

Organic azides are widely used in the total synthesis of natural products, medicinal chemistry and material chemistry. Azides tend to release molecular nitrogen to construct nitrogen-containing heterocycles or amino compounds. However, the retention of azide is necessary in the critical synthesis steps of some natural products. The types of C-N3 retention in organic reactions are summarized, including cycloaddition, addition with unsaturated bond, Winstein rearrangement and 1,2-migration. Keywords organic azide; C-N3 bond; cycloaddition; rearrangement 有机叠氮化合物在 1864 年由德国化学家 Grieß 首次 合成出来 [1] , 它是一类具有 N＝N ＋ ＝N -结构的多功能化 合物, 广泛分布于生物活性分子中 [2] , 且在生物正交性 实验中发挥了重要作用 [3] . 有机叠氮化合物 [4] 具有独特 的物理化学性质和较高的反应活性, 可以进行多种多样 的转化, 是非常有价值的有机合成中间体, 且合成过程 简单, 易获得. 叠氮化合物参与的反应主要包括: (1) Click 反应, 叠氮的偶极特性使其可以与炔进行 1,3-偶极 环加成反应, 生成 1,2,3-三氮唑 [5] (Scheme 1, a), 此类反 应被广泛应用于药物合成、生物化学以及材料化学等领 域 [6] ; (2) Schmidt 重排, 叠氮化合物与醛基或羰基 [7a-7g] 反应得到酰胺类化合物(Scheme 1, b), 也可以与碳正离 子 [7h-7j] 反应, 再经氮气脱除过程得到含氮杂环; (3) Curtius 重排, 酰基叠氮在加热条件下经过脱氮气/重排生成 异氰酸酯, 随后与水反应可得到伯胺, 与胺反应可得到 脲, 与醇反应可得到氨基甲酸酯 [8] (Scheme 1, c); (4) Staudinger 还原, 叠氮与膦反应脱除氮气后得到氮杂膦 叶立德, 再与水反应得到胺 [9a] (Scheme 1, d).

Visible-Light-Mediated Azidation of α-Diazoesters with TMSN3 via Direct Photoexcitation and SH2 Mechanism

“…Organic azides are extensively used in pharmaceuticals, bioorthogonal labeling, biological imaging, and materials synthesis . Meanwhile, they are versatile organic synthons to synthesize N-heterocycles, amines and miscellaneous compounds via diverse transformations, such as well-known azide–alkyne cycloaddition (AAC), C–H amination, and C–N 3 retention reactions . With respect to the synthesis of valuable organic azides, azidation is one of the most straightforward approaches.…”