Yu Yi-Zhe, Su Hong-Yi, Zhuo Chun-Xiang
State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province, and College of Chemistry and Chemical Engineering, Xiamen University, 361005, Xiamen, P. R. China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, P. R. China.
Angew Chem Int Ed Engl. 2024 Dec 16;63(51):e202412299. doi: 10.1002/anie.202412299. Epub 2024 Oct 30.
The multi-substituted anilines are widely found in organic synthesis, medicinal chemistry and material science. The quest for robust and efficient methods to construct a diverse array of these compounds using readily accessible starting materials under simple reaction conditions is of utmost importance. Here, we report an unprecedented and efficient approach for the synthesis of 2,4-di and 2,4,6-trisubstituted anilines. With a simple molybdenum(VI) catalyst, a wide range of 2,4-di and 2,4,6-trisubstituted anilines were efficiently prepared in generally good to excellent yields from readily accessible ynones and allylic amines. The synthetic potential of this methodology was further underscored by its applications in several synthetic transformations, gram-scale reactions, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this aniline formation might involve a cascade of aza-Michael addition, [1,6]-proton shift, cyclization, dehydration, 6π-electrocyclization, and aromatization. This novel strategy provided a robust, simple, and modular approach for the syntheses of various valuable di- or trisubstituted anilines, some of which were otherwise challenging to access.
多取代苯胺广泛存在于有机合成、药物化学和材料科学领域。寻求在简单反应条件下使用易于获得的起始原料构建各种此类化合物的稳健且高效的方法至关重要。在此，我们报道了一种前所未有的高效合成2,4-二取代和2,4,6-三取代苯胺的方法。使用一种简单的钼(VI)催化剂，从易于获得的炔酮和烯丙基胺出发，以普遍良好至优异的产率高效制备了多种2,4-二取代和2,4,6-三取代苯胺。该方法在多种合成转化、克级反应以及生物活性分子的衍生化中的应用进一步突出了其合成潜力。初步机理研究表明，这种苯胺的形成可能涉及氮杂-Michael加成、[1,6]-质子迁移、环化、脱水、6π-电环化和芳构化的串联反应。这种新颖的策略为各种有价值的二取代或三取代苯胺的合成提供了一种稳健、简单且模块化的方法，其中一些苯胺的合成在其他情况下具有挑战性。
