化学
对映选择合成
氰化
激进的
催化作用
组合化学
基质(水族馆)
氢原子萃取
对映体
试剂
对映体过量
铜
有机合成
光化学
药物化学
有机化学
海洋学
地质学
作者
Wen Zhang,Fei Wang,Scott D. McCann,Dinghai Wang,Pinhong Chen,Shannon S. Stahl,Guosheng Liu
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2016-09-02
卷期号:353 (6303): 1014-1018
被引量:503
标识
DOI:10.1126/science.aaf7783
摘要
Direct methods for stereoselective functionalization of sp3-hybridized carbon-hydrogen [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 formation 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 to 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.
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