Radical Arylation of Phenols, Phenyl Ethers, and Furans
Radical Arylation of Phenols, Phenyl Ethers, and Furans
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DOI：
10.1002/chem.200902927
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Heinrich, Markus R.
中科院分区：
文献类型：
--
作者：
Wetzel, Alexander;Pratsch, Gerald;Heinrich, Markus R.
对位取代苯酚和苯基醚的自由基芳基化反应在羟基或烷氧基的邻位进行，具有良好的区域选择性。该反应是用芳烃重氮盐作为芳基源，氯化钛（III）作为还原剂，稀盐酸作为溶剂进行的。取代的联芳基化合物是由羟基和烷氧基取代的苄胺、苯乙胺和芳香族氨基酸得到的。所描述的方法提供了一种快速、有效和具有成本效益的新途径来获得双取代基官能化的联苯醇和醚。游离酚羟基、芳香族和脂肪族胺以及氨基酸亚结构耐受良好。该方法适用性的两个例子是β-分泌酶抑制剂的部分合成和钙通道调节剂的合成。
Radical arylations of para-substituted phenols and phenyl ethers proceeded with good regioselectivity at the ortho position with respect to the hydroxy or alkoxy group. The reactions were conducted with arenediazonium salts as the aryl radical source, titanium(III) chloride as the reductant, and diluted hydrochloric acid as the solvent. Substituted biaryls were obtamed from hydroxy- and alkoxy-substituted benzylamines, phenethyl-amines, and aromatic amino acids. The methodology described offers a fast, efficient, and cost-effective new access to diversely functionalized biphenyl alcohols and ethers. Free phenolic hydroxy groups, aromatic and aliphatic amines, as well as amino acid substructures, are well tolerated. Two examples for the applicability of the methodology are the partial synthesis of a beta-secretase inhibitor and the synthesis of a calcium-channel modulator.