Yu Yi-Zhe, Bai Jin, Peng Jia-Min, Yao Jia-Sheng, 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, Xiamen 361005, People's Republic of China.
Shenzhen Research Institute of Xiamen University, Shenzhen 518057, People's Republic of China.
J Am Chem Soc. 2023 Apr 26;145(16):8781-8787. doi: 10.1021/jacs.3c01330. Epub 2023 Mar 17.
The substituted benzene derivatives are essential to organic synthesis, medicinal chemistry, and material science. However, the 1,3-di- and 1,3,5-trisubstituted benzenes are far less prevalent in small-molecule drugs than other substitution patterns, likely due to the lack of robust, efficient, and convenient synthetic methods. Here, we report a Mo-catalyzed intermolecular deoxygenative benzene-forming reaction of readily available ynones and allylic amines. A wide range of unsymmetric and unfunctionalized 1,3-di- and 1,3,5-trisubstituted benzenes were obtained in up to 88% yield by using a commercially available molybdenum catalyst. The synthetic potential of the method was further illustrated by synthetic transformations, a scale-up synthesis, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this benzene-forming process might proceed through a Mo-catalyzed aza-Michael addition/[1,5]-hydride shift/cyclization/aromatization cascade. This strategy not only provided a facile, robust, and modular approach to various -substituted benzene derivatives but also demonstrated the potential of molybdenum catalysis in the challenging intermolecular deoxygenative cross-coupling reactions.
取代苯衍生物对于有机合成、药物化学和材料科学至关重要。然而，1,3-二取代和1,3,5-三取代苯在小分子药物中的普遍性远低于其他取代模式，这可能是由于缺乏强大、高效且便捷的合成方法。在此，我们报道了一种钼催化的、由易得的炔酮和烯丙基胺进行的分子间脱氧成苯反应。通过使用市售钼催化剂，可获得产率高达88%的多种不对称且未官能化的1,3-二取代和1,3,5-三取代苯。该方法的合成潜力通过合成转化、放大合成以及生物活性分子的衍生化得到进一步说明。初步机理研究表明，这种成苯过程可能通过钼催化的氮杂迈克尔加成/[1,5]-氢迁移/环化/芳构化级联反应进行。该策略不仅为各种取代苯衍生物提供了一种简便、强大且模块化的方法，还展示了钼催化在具有挑战性的分子间脱氧交叉偶联反应中的潜力。
