Selective formation of γ-lactams via C-H amidation enabled by tailored iridium catalysts
Selective formation of γ-lactams via C-H amidation enabled by tailored iridium catalysts
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DOI：
10.1126/science.aap7503
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发表时间：
2018-03-02
期刊：
影响因子：
56.9
通讯作者：
Chang, Sukbok
中科院分区：
文献类型：
--
作者：
Hong, Seung Youn;Park, Yoonsu;Chang, Sukbok
传统上，金属氮烯分子内插入碳-氢键形成γ-内酰胺环受到竞争性异氰酸酯形成的阻碍。我们报告了应用理论和机理研究来优化一类五甲基环戊二烯基铱（III）催化剂以抑制这种竞争途径。密度泛函理论计算表明，调节辅助二齿配体的立体电子特性使其更具电子供给性，以降低有利于所需反应的C-H插入势垒。这些催化剂可通过 sp(3) 和 sp(2) C-H 酰胺化以优异的选择性将各种 1,4,2-二恶唑-5-酮（可轻松从羧酸中获得的羰基氮烯前体）转化为相应的 γ-内酰胺。氨基酸衍生物和其他生物活性分子的成功后期功能化进一步证明了该方法的威力。
Intramolecular insertion of metal nitrenes into carbon-hydrogen bonds to form gamma-lactam rings has traditionally been hindered bycompeting isocyanate formation. We report the application of theory and mechanism studies to optimize a class of pentamethylcyclopentadienyl iridium(III) catalysts for suppression of this competing pathway. Modulation of the stereoelectronic properties of the auxiliary bidentate ligands to be more electron-donating was suggested by density functional theory calculations to lower the C-H insertion barrier favoring the desired reaction. These catalysts transform a wide range of 1,4,2-dioxazol-5-ones, carbonylnitrene precursors easily accessible from carboxylic acids, into the corresponding gamma-lactams via sp(3) and sp(2) C-H amidation with exceptional selectivity. The power of this method was further demonstrated by the successful late-stage functionalization of amino acid derivatives and other bioactive molecules.