东北师范大学张前团队报道了铜催化末端炔的区域发散不对称双官能化。相关研究成果于2024年6月25日发表在国际顶尖学术期刊《德国应用化学》。

该文中，研究人员描述了通过级联硼氢化和烯丙基化过程对配体控制的、铜催化的末端炔烃的区域会聚不对称二官能化的第一个例子。由（R）-DTBM-Segphos和CuBr组成的催化体系可以有效地实现芳基末端炔烃的不对称1，1-二官能化，而配体转换为（S，S）-Ph-BPE可以仅导致不对称1，2-二官能化。此外，烷基取代的末端炔烃，特别是工业上相关的乙炔和丙炔，也是不对称1,1-二官能化的有效原料。

该方案具有良好的官能团耐受性、广泛的底物范围（>150个实例）和温和的反应条件。研究人员还展示了这种方法在复杂生物活性分子的后期功能化和简化天然产物（bruguierol A）关键中间体的合成路线方面的价值。结合DFT计算的机制研究提供了，对这种配体控制的区域和立体选择性的机制和起源的深入了解。

附：英文原文

Title: Copper-Catalyzed Regiodivergent Asymmetric Difunctionalization of Terminal Alkynes

Author: Simin Wang, Kexin Chen, Junbo Niu, Xiaobing Guo, Xiuping Yuan, Jianjun Yin, Bo Zhu, Dazhen Shi, Wei Guan, Tao Xiong, Qian Zhang

Issue&Volume: 2024-06-25

Abstract: We herein describe the first example of ligand-controlled, copper-catalyzed regiodivergent asymmetric difunctionalization of terminal alkynes through a cascade hydroboration and hydroallylation process. The catalytic system, consisting of (R)-DTBM-Segphos and CuBr, could efficiently achieve asymmetric 1,1-difunctionalization of aryl terminal alkynes, while ligand switching to (S,S)-Ph-BPE could result in asymmetric 1,2-difunctionalization exclusively. In addition, alkyl substituted terminal alkynes, especially industrially relevant acetylene and propyne, were also valid feedstocks for asymmetric 1,1-difunctionalization. This protocol is characterized by good functional group tolerance, a broad scope of substrates (> 150 examples), and mild reaction conditions. We also showcase the value of this method in the late-stage functionalization of complicated bioactive molecules and simplifying the synthetic routes toward the key intermediacy of natural product (bruguierol A). Mechanistic studies combined with DFT calculations provide insight into the mechanism and origins of this ligand-controlled regio- and stereoselectivity.

DOI: 10.1002/anie.202410833

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202410833