A general asymmetric copper-catalysed Sonogashira C(sp3)-C(sp) coupling
A general asymmetric copper-catalysed Sonogashira C(sp3)-C(sp) coupling
复制标题
DOI：
10.1038/s41557-019-0346-2
复制
发表时间：
2019-12-01
期刊：
影响因子：
21.8
通讯作者：
Liu, Xin-Yuan
中科院分区：
文献类型：
--
作者：
Dong, Xiao-Yang;Zhang, Yu-Feng;Liu, Xin-Yuan
Sonogashira偶联的持续发展使其成为一种良好建立的和通用的反应，用于直接形成C-C键，锻造广泛有用的官能化分子的碳骨架。然而，不对称Sonogashira偶联，特别是C（sp（3））-C（sp）键的形成，仍然在很大程度上未被探索。在这里，我们展示了广泛的末端炔和外消旋烷基卤（>120个实例）的一般立体会聚Sonogashira C（sp（3））-C（sp）交叉偶联，其通过使用手性金鸡纳生物碱基P，N-配体的铜催化的自由基参与的炔基化来实现。工业相关的乙炔和丙炔被成功纳入，为可扩展和经济的合成应用奠定了基础。该方法的潜在用途已在立体富集生物活性或功能分子衍生物、药用化合物和天然产物的简易合成中得到证实，这些衍生物具有一系列手性C（sp（3））-C（sp/sp（2）/sp（3）键。这项工作强调了自由基物种的重要性，为发展antireoconvergent转换。
Continued development of the Sonogashira coupling has made it a well established and versatile reaction for the straightforward formation of C-C bonds, forging the carbon skeletons of broadly useful functionalized molecules. However, asymmetric Sonogashira coupling, particularly for C(sp(3))-C(sp) bond formation, has remained largely unexplored. Here we demonstrate a general stereoconvergent Sonogashira C(sp(3))-C(sp) cross-coupling of a broad range of terminal alkynes and racemic alkyl halides (>120 examples) that are enabled by copper-catalysed radical-involved alkynylation using a chiral cinchona alkaloid-based P,N-ligand. Industrially relevant acetylene and propyne are successfully incorporated, laying the foundation for scalable and economic synthetic applications. The potential utility of this method is demonstrated in the facile synthesis of stereoenriched bioactive or functional molecule derivatives, medicinal compounds and natural products that feature a range of chiral C(sp(3))-C(sp/sp(2)/sp(3)) bonds. This work emphasizes the importance of radical species for developing enantioconvergent transformations.