Chiral donor–acceptor azetines as powerful reactants for synthesis of amino acid derivatives
Chiral donor–acceptor azetines as powerful reactants for synthesis of amino acid derivatives
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DOI：
10.1038/s41467-019-13326-8
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发表时间：
2019-11
影响因子：
16.6
通讯作者：
Kostiantyn O. Marichev;Kuiyong Dong;Lynée A. Massey;Yongming Deng;Luca De Angelis;Kan Wang;H. Arman;M. Doyle
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文献类型：
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作者：
Kostiantyn O. Marichev;Kuiyong Dong;Lynée A. Massey;Yongming Deng;Luca De Angelis;Kan Wang;H. Arman;M. Doyle
胺和醇的偶联反应在化学和生物学中具有重要的应用。这些转化通常涉及使用活化为亲电试剂的试剂，亲核试剂偶联在其上导致形成碳-氮键或碳-氧键。已经开发了几种有前途的试剂和程序，以实现这些键形成过程中的高产率与优异的立体控制，但很少提供直接耦合没有催化剂的干预。本文报道了通过烯醇重氮乙酸酯与氮杂叶立德的高对映选择性[3 + 1]-环加成反应合成手性给体-受体氮杂环丁烷类化合物，并通过3-氮杂环丁烷酮与氮、氧亲核试剂选择性偶联生成氨基酸衍生物，包括肽和天然产物。整个过程是一般的一个广谱的亲核试剂，具有高度的电子和空间选择性，并保留了原始吖丙啶的对映体纯度。
Coupling reactions of amines and alcohols are of central importance for applications in chemistry and biology. These transformations typically involve the use of a reagent, activated as an electrophile, onto which nucleophile coupling results in the formation of a carbon-nitrogen or a carbon–oxygen bond. Several promising reagents and procedures have been developed to achieve these bond forming processes in high yields with excellent stereocontrol, but few offer direct coupling without the intervention of a catalyst. Herein, we report the synthesis of chiral donor–acceptor azetines by highly enantioselective [3 + 1]-cycloaddition of enoldiazoacetates with aza-ylides and their selective coupling with nitrogen and oxygen nucleophiles via 3-azetidinones to form amino acid derivatives, including those of peptides and natural products. The overall process is general for a broad spectrum of nucleophiles, has a high degree of electronic and steric selectivity, and retains the enantiopurity of the original azetine.