Gu Rui, Feng Xiujuan, Bao Ming, Zhang Xuan
School of Chemistry and Materials Science, Institute of Advanced Materials and Flexible Electronics (IAMFE), Nanjing University of Information Science and Technology, 219 Ningliu Road, Nanjing, 210044, China.
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China.
Nat Commun. 2023 Nov 23;14(1):7669. doi: 10.1038/s41467-023-43561-z.
Carbon-introducing difunctionalization of C-C double bonds enabled by transition-metal catalysis is one of most straightforward and efficient strategies to construct C-C and C-X bonds concurrently from readily available feedstocks towards structurally diverse molecules in one step; however, analogous difunctionalization for introducing germanium group and other functionalities remains elusive. Herein, we describe a nickel-catalyzed germylative alkylation of activated olefins with easily accessible primary, secondary and tertiary alkyl bromides and chlorogermanes as the electrophiles to form C-Ge and C-C bonds simultaneously. This method provides a modular and facile approach for the synthesis of a broad range of alkylgermanes with good functional group compatibility, and can be further applied to the late-stage modification of natural products and pharmaceuticals, as well as ligation of drug fragments. More importantly, this platform enables the expedient synthesis of germanium substituted ospemifene-Ge-OH, which shows improved properties compared to ospemifene in the treatment of breast cancer cells, demonstrating high potential of our protocol in drug development.
过渡金属催化实现的碳碳双键引入碳的双官能团化是从易得原料一步构建碳碳键和碳-杂原子键以合成结构多样分子的最直接有效的策略之一；然而，引入锗基团和其他官能团的类似双官能团化方法仍然难以实现。在此，我们报道了一种镍催化的活化烯烃与易于获得的伯、仲、叔烷基溴以及氯锗烷作为亲电试剂的锗基烷基化反应，可同时形成碳-锗键和碳-碳键。该方法为合成具有良好官能团兼容性的多种烷基锗提供了一种模块化且简便的方法，并且可进一步应用于天然产物和药物的后期修饰以及药物片段的连接。更重要的是，该平台能够便捷地合成锗取代的奥司米芬-Ge-OH，其在治疗乳腺癌细胞方面相较于奥司米芬显示出改善的性能，证明了我们的方法在药物开发中的巨大潜力。
