Copper-catalysed benzylic C-H coupling with alcohols via radical relay enabled by redox buffering
Copper-catalysed benzylic C-H coupling with alcohols via radical relay enabled by redox buffering
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DOI：
10.1038/s41929-020-0425-1
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发表时间：
2020-02-24
期刊：
影响因子：
37.8
通讯作者：
Stahl, Shannon S.
中科院分区：
文献类型：
--
作者：
Hu, Huayou;Chen, Si-Jie;Stahl, Shannon S.
交叉偶联反应能够快速、收敛地合成多种分子，为现代化学合成奠定了基础。最广泛使用的方法采用sp(2)杂化偶联伙伴，如芳基卤化物或相关的预功能化底物。在这里，我们证明了铜催化的苯基C-H键与醇的氧化交叉偶联产生苯醚，通过氧化还原缓冲策略在整个反应过程中保持铜催化剂的活性。反应采用C-H底物作为限制试剂，并且相对于两个偶联伙伴表现出广泛的范围。这种直接对C(sp(3))-H键进行位点选择性功能化的方法为有机分子的高效三维多样化提供了基础，并将在有机合成中得到广泛应用，特别是在药物化学应用中。
Cross-coupling reactions enable rapid, convergent synthesis of diverse molecules and provide the foundation for modern chemical synthesis. The most widely used methods employ sp(2)-hybridized coupling partners, such as aryl halides or related pre-functionalized substrates. Here, we demonstrate copper-catalysed oxidative cross-coupling of benzylic C-H bonds with alcohols to afford benzyl ethers, enabled by a redox buffering strategy that maintains the activity of the copper catalyst throughout the reaction. The reactions employ the C-H substrate as the limiting reagent and exhibit broad scope with respect to both coupling partners. This approach to direct site-selective functionalization of C(sp(3))-H bonds provides the basis for efficient three-dimensional diversification of organic molecules and should find widespread utility in organic synthesis, particularly for medicinal chemistry applications.