Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source
Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source
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DOI：
10.1021/jacs.0c02805
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发表时间：
2020-04-22
影响因子：
15
通讯作者：
Doyle, Abigail G.
中科院分区：
文献类型：
--
作者：
Kariofillis, Stavros K.;Shields, Benjamin J.;Doyle, Abigail G.
有机卤化物的甲基化是一种有价值的转化，但通常需要苛刻的反应条件或试剂。我们报道了一种使用镍/光氧化还原催化对（杂）芳基氯化物进行甲基化的自由基方法，其中原甲酸三甲酯（一种常见的实验室溶剂）作为甲基源。这种方法允许在早期和后期对（杂）芳基氯化物和酰氯进行甲基化，且具有广泛的官能团兼容性。机理研究表明，原甲酸三甲酯通过氯介导的氢原子转移产生的三级自由基的β-断裂作为甲基自由基的来源。
Methylation of organohalides represents a valuable transformation, but typically requires harsh reaction conditions or reagents. We report a radical approach for the methylation of (hetero)aryl chlorides using nickel/photoredox catalysis wherein trimethyl orthoformate, a common laboratory solvent, serves as a methyl source. This method permits methylation of (hetero)aryl chlorides and acyl chlorides at an early and late stage with broad functional group compatibility. Mechanistic investigations indicate that trimethyl orthoformate serves as a source of methyl radical via beta-scission from a tertiary radical generated upon chlorine-mediated hydrogen atom transfer.