Metalation of nitroaromatics with in situ electrophiles
Metalation of nitroaromatics with in situ electrophiles
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DOI：
10.1021/jo961839t
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发表时间：
1997-02-07
影响因子：
3.6
通讯作者：
Scheuermeyer, F
中科院分区：
文献类型：
--
作者：
Black, WC;Guay, B;Scheuermeyer, F
取代芳烃的定向邻位金属化反应是将官能团引入芳核的一种有效方法。金属化化学的一个局限是它与硝基不相容。通常用于金属化的烷基锂通过电子转移来还原硝基，通常会导致底物的分解。在低温下用金属卤素交换反应制备（硝基）锂已有报道，但这些反应并不普遍，所得到的芳基锂容易通过氧化还原机制分解。硝基芳烃是一种有价值的合成中间体，因为它们易于合成，能够激活亲核芳香取代中的离去基，并且易于还原成多功能胺衍生物。因此，与硝基功能兼容的DoM化学将是一个很大的优势。本文讨论了电子缺陷底物的硝基芳香族金属化问题，并报道了与该反应机制有关的观察结果。硝基和碳中心阴离子的明显不相容性促使我们探索减少这两个物种之间接触的方法。硝基应该显著提高附近芳香质子的酸度，允许使用比通常的烷基锂更温和的碱。在活化芳香体系中，锂酰胺碱被用于DoM化学，有望避免烷基锂碱的一些氧化还原问题。另一个问题是由中间体（硝基）锂的固有不稳定性引起的。这可以通过使用原位亲电剂来最小化（硝基）锂中间体的寿命来解决。
The directed ortho metalation (DoM) reaction of substituted aromatics is a powerful method of introducing functional groups to an aromatic nucleus. 1 One limitation of metalation chemistry is its incompatibility with the nitro group. Reduction of the nitro group by electron transfer from the alkyllithiums often used in metalations generally results in decomposition of the substrates. The preparation of (nitroaryl) lithium species by metalhalogen exchange reactions at low temperatures has been reported, 2 but these reactions are not general, and the resulting aryllithiums readily decompose by redox mechanisms.Nitroaromatics are valuable synthetic intermediates due to their ease of synthesis, their ability to activate leaving groups in nucleophilic aromatic substitution, and their ready reduction to versatile amine derivatives. As a result, DoM chemistry compatible with nitro functionality would be a great advantage. This paper addresses the nitroaromatic metalation problem for electrondeficient substrates and reports observations pertinent to the mechanism of this reaction. The apparent incompatibility of nitro groups and carbon-centered anions prompted us to explore methods of minimizing contact between these two species. The nitro group should significantly enhance the acidity of nearby aromatic protons, allowing the use of a base milder than the usual alkyllithiums. Lithium amide bases have been used for DoM chemistry in activated aromatic systems3 and would be expected to avoid some of the redox problems associated with alkyllithium bases. An additional problem is posed by the inherent instability of the intermediate (nitroaryl) lithium species. This can be addressed by the use of an in situ electrophile4 to minimize the lifetime of the (nitroaryl) lithium intermediate.