Umpolung reactivity in amide and peptide synthesis.
Umpolung reactivity in amide and peptide synthesis.
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酰胺官能团是 Nature 的关键功能和结构元素之一，尤其是在肽中。酰胺也是制备多种治疗性小分子的关键中间体。尽管氧化和基于自由基的方法是代表性的替代方法，但使用可用方法的其构建主要集中于脱水方法。在大多数例子中的碳-氮键形成步骤中，碳和氮分别具有亲电子和亲核特性。在这里，我们表明，在湿 THF 中用亲电子碘源活化胺和硝基烷烃可以直接产生酰胺产物。初步观察结果支持一种机械结构，其中相对于传统方法，在 C-N 键形成过程中反应物极性发生反转（反极性）。使用硝基烷烃作为酰基阴离子等价物为酰胺和肽合成提供了一种概念上创新的方法，并且最终可能提供完全依赖于对映选择性方法的有效肽合成。
The amide functional group is one of Nature’s key functional and structural elements, most notably within peptides. Amides are also key intermediates in the preparation of a diverse range of therapeutic small molecules. Its construction using available methods focuses principally upon dehydrative approaches, although oxidative and radical-based methods are representative alternatives. During the carbon-nitrogen bond forming step in most every example, the carbon and nitrogen bear electrophilic and nucleophilic character, respectively. Here we show that activation of amines and nitroalkanes with an electrophilic iodine source in wet THF can lead directly to amide products. Preliminary observations support a mechanistic construct in which reactant polarity is reversed (umpolung) during C-N bond formation relative to traditional approaches. The use of nitroalkanes as acyl anion equivalents provides a conceptually innovative approach to amide and peptide synthesis, and one that might ultimately provide for efficient peptide synthesis that is fully reliant on enantioselective methods.
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影响因子：
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