Copper-Catalyzed Chan-Lam Cyclopropylation of Phenols and Azaheterocycles
Copper-Catalyzed Chan-Lam Cyclopropylation of Phenols and Azaheterocycles
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DOI：
10.1021/acs.joc.7b03100
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发表时间：
2018-04-06
影响因子：
3.6
通讯作者：
Engle, Keary M.
中科院分区：
文献类型：
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作者：
Derosa, Joseph;O'Duill, Miriam L.;Engle, Keary M.
含有环丙烷-杂原子键的小分子通常在药物化学活动中需要，但使用现有方法制备是有问题的。为了解决这个问题，开发了使用环丙基三氟硼酸钾的可扩展的Chan-Lam环丙基化反应。与苯酚亲核试剂，反应的影响O-环丙基化，而与2-吡啶酮，2-羟基苯并咪唑，和2-氨基吡啶的反应带来N-环丙基化。该转化由Cu（OAc）（2）和1，10-菲咯啉催化，并使用1大气压的O-2作为末端氧化剂。该方法在操作上便于进行，并且为合成带有一系列官能团的环丙基芳基醚和环丙胺衍生物提供了简单的、策略性的断开。
Small molecules containing cyclopropane-heteroatom linkages are commonly needed in medicinal chemistry campaigns yet are problematic to prepare using existing methods. To address this issue, a scalable Chan-Lam cydopropylation reaction using potassium cydopropyl tri-fluoroborate has been developed. With phenol nucleophiles, the reaction effects O-cyclopropylation, whereas with 2-pyridones, 2-hydroxybenzimidazoles, and 2-aminopyridines the reaction brings about N-cydopropylation. The transformation is catalyzed by Cu(OAc)(2) and 1,10-phenanthroline and employs 1 atm of O-2 as the terminal oxidant. This method is operationally convenient to perform and provides a simple, strategic disconnection toward the synthesis of cydopropyl aryl ethers and cydopropyl amine derivatives bearing an array of functional groups.