Chemical reactions that reliably join two molecular fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochemicals1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho versus meta versus para) is currently achievable only in transition-metal-catalysed processes and requires halogen- or boron-containing substrates3–6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C–H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs in nature and is often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon–nitrogen (C–N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using the well established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chemistry. We demonstrate the utility of this C–N coupling protocol by preparing commercial medicines and by the late-stage amination–aromatization of natural products, steroids and terpene feedstocks. A dual cobalt and photocatalysis system provides a way to assemble anilines from cyclohexanones and amines by progressively dehydrating the intermediate imine.

中文翻译：

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苯胺合成的光化学脱氢策略

将两个分子片段可靠地连接在一起（交叉偶联）的化学反应对于药物和农用化学品的发现和制造至关重要 1,2。在特定和预定位置（邻位对间位对对位）将胺引入官能化芳烃目前只能在过渡金属催化过程中实现，并且需要含卤素或硼的底物3-6。在芳族单元周围引入这些基团取决于该方法的固有反应特性（亲电卤化或 C-H 硼化），因此通常不可能选择性靶向所有位置。在这里，我们报告了一种用于构建苯胺的非规范交叉偶联方法，利用饱和环己酮作为芳基亲电子试剂的替代品。胺和羰基化合物之间的缩合是自然界中经常发生的过程，并且经常被（生物）有机化学家使用 7，能够形成预定的和位点选择性的碳 - 氮（C-N）键，而光氧化还原 - 和钴 -基于催化系统的环己烯环在生成苯胺的过程中逐渐去饱和。考虑到功能化环己酮很容易通过使用完善的羰基反应性进行完全区域控制，这种方法绕过了芳族化学中一些常见的选择性问题。我们通过制备商业药物和天然产物、类固醇和萜烯原料的后期胺化-芳构化来证明这种 C-N 偶联方案的效用。