Zhang Yongsheng, Wang Jincheng, He Xiaoyan, Peng Shilin, Yuan Lei, Huang Gang, Guo Yongjin, Lu Xiuhong
Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, 201318, P. R. China.
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Adv Sci (Weinh). 2025 Jan;12(1):e2411788. doi: 10.1002/advs.202411788. Epub 2024 Oct 29.
Cyclopropane fragments, which widely exist in marketed drugs and natural products, can confer special pharmacological properties to small-molecule drugs. Therefore, developing methods to construct cyclopropanes is of great significance. Nevertheless, the introduction of cyclopropane primarily relies on already-formed cyclopropyl groups, which significantly restricts the diversity of cyclopropane skeletons. Late-stage direct cyclopropanation is still a challenging task. Herein, a photo-induced intermolecular deoxycyclopropanation reaction that employs alcohols as substrates, and 1 mol.% of 2,3,5,6-tetrakis(carbazol-9-yl)-1,4-dicyanobenzene (4CzTPN) as organophotocatalyst is reported. This method proceeds with high transformation efficiency (up to 98% yield) and exhibits broad functional group tolerance, such as primary, secondary, and tertiary alcohols as well as various activated β-halogenated alkenes. This process is mild, easy to operate, and has low equipment requirements. The power of this technology is demonstrated by the late-stage functionalization of five marketed drugs and five natural products.
环丙烷片段广泛存在于市售药物和天然产物中，可为小分子药物赋予特殊的药理特性。因此，开发构建环丙烷的方法具有重要意义。然而，环丙烷的引入主要依赖于已形成的环丙基，这极大地限制了环丙烷骨架的多样性。后期直接环丙烷化仍然是一项具有挑战性的任务。在此，报道了一种光诱导的分子间脱氧环丙烷化反应，该反应以醇为底物，1 mol%的2,3,5,6-四（咔唑-9-基）-1,4-二氰基苯（4CzTPN）作为有机光催化剂。该方法具有高转化效率（产率高达98%），并表现出广泛的官能团耐受性，如伯醇、仲醇和叔醇以及各种活化的β-卤代烯烃。该过程温和、易于操作且设备要求低。五种市售药物和五种天然产物的后期官能化证明了该技术的强大之处。
