Interaction between Divalent Copper Fluoride and Carboxamide Group Enabling Stereoretentive Fluorination of Tertiary Alkyl Halides
Interaction between Divalent Copper Fluoride and Carboxamide Group Enabling Stereoretentive Fluorination of Tertiary Alkyl Halides
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二价氟化铜与羧酰胺基团之间的相互作用实现叔烷基卤化物的立体保留氟化
DOI：
10.1002/anie.202301343
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Nishikata Takashi
中科院分区：
文献类型：
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作者：
Tsuchiya Naoki;Yamamoto Tetsuhiro;Akagawa Hiroki;Nishikata Takashi
在本文中，我们报道了一种铜催化的立体特异性双链反应，其涉及CsF和α-溴代甲酰胺作为叔烷基来源，与涉及立体转化SN 2反应的传统立体特异性路线不同，其进行保留立体化学。开发的立体定向Cu催化反应是合成具有高度密集立体碳中心的氟化分子的最有效方法之一。机理研究表明，CuF 2和Cs盐的组合反应性是完成催化循环所必需的。我们的催化体系只与叔烷基溴反应，不与伯烷基溴反应，表明这种立体定向的催化方法适用于合成具有立体限定的含F叔碳立体异构中心的氟化结构单元。
Herein, we report a copper‐catalyzed stereospecific fluorination involving CsF and α‐bromocarboxamides as tertiary alkyl sources that, unlike traditional stereospecific routes involving stereoinversive SN2 reactions, proceeds with retention of stereochemistry. The developed stereospecific Cu‐catalyzed reaction is among the most efficient methods for synthesizing fluorinated molecules that possess highly congested stereogenic carbon centers. Mechanistic studies revealed that the combined reactivity of CuF2and Cs salt is essential for completing the catalytic cycle. Our catalytic system underwent fluorination exclusively with tertiary alkyl bromides and did not react with primary alkyl bromides, indicating that this stereospecific fluorination methodology is suitable for synthesizing fluorinated building blocks possessing stereo‐defined F‐containing tertiary carbon stereogenic center.