Enantioselective cyanation of benzylic C-H bonds via copper-catalyzed radical relay.
Enantioselective cyanation of benzylic C-H bonds via copper-catalyzed radical relay.
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通过铜催化自由基中继对苯甲基 C-H 键进行对映选择性氰化
DOI：
10.1126/science.aaf7783
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发表时间：
2016-09-02
期刊：
影响因子：
--
通讯作者：
Liu G
中科院分区：
文献类型：
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作者：
Zhang W;Wang F;McCann SD;Wang D;Chen P;Stahl SS;Liu G
在复杂有机分子中立体选择性官能化C（sp3）-H键的直接方法可以促进更有效地制备治疗剂和农用化学品。在这里，我们报告了一个铜催化的自由基中继途径的苄基C-H键的不对称转化为苄腈。氢原子提取提供非手性苄基自由基，其在与手性铜催化剂反应时经历不对称C（sp3）-CN键。该反应在室温下以苄基底物作为限制试剂有效进行，表现出宽的底物范围和高的对映体选择性（通常90-99%对映体过量），并提供作为重要生物活性分子的关键前体的产物。机理研究提供了可扩散的有机自由基的证据，并强调了这些反应与通过自由基反弹途径操作的酶和其他催化剂介导的C-H氧化之间的差异。
Direct methods for stereoselective functionalization of C(sp3)–H bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C–H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp3)–CN bond upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90-99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C–H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways.