A Metallaphotoredox Strategy for the Cross-Electrophile Coupling of α-Chloro Carbonyls with Aryl Halides
A Metallaphotoredox Strategy for the Cross-Electrophile Coupling of α-Chloro Carbonyls with Aryl Halides
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DOI：
10.1002/anie.201909072
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发表时间：
2019-09-05
影响因子：
16.6
通讯作者：
MacMillan, David W. C.
中科院分区：
文献类型：
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作者：
Chen, Tiffany Q.;MacMillan, David W. C.
在这里，我们证明了金属光氧化还原催化的交叉亲电偶联机制提供了一个统一的方法，用于不同的活化烷基氯，包括α-氯酮，α-氯酯，α-氯酰胺，α-氯羧酸，苄氯的α-芳基化。这种策略，这是有效的各种各样的芳基溴偶联合作伙伴，是基于卤素原子抽象/镍自由基捕获机制，是普遍成功的广泛的羰基底物。芳基乙酸产物的构建和使用进一步实现了用于递送用于药物化学的有价值的结构单元的两步方案，例如芳基二氟甲基和二芳基甲烷基序。
Here, we demonstrate that a metallaphotoredox-catalyzed cross-electrophile coupling mechanism provides a unified method for the alpha-arylation of diverse activated alkyl chlorides, including alpha-chloroketones, alpha-chloroesters, alpha-chloroamides, alpha-chlorocarboxylic acids, and benzylic chlorides. This strategy, which is effective for a wide variety of aryl bromide coupling partners, is predicated upon a halogen atom abstraction/nickel radical-capture mechanism that is generically successful across an extensive range of carbonyl substrates. The construction and use of arylacetic acid products have further enabled two-step protocols for the delivery of valuable building blocks for medicinal chemistry, such as aryldifluoromethyl and diarylmethane motifs.