Zhang Yan, Zheng Jing, Cui Sunliang
Institute of Materia Medica and College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, China.
J Org Chem. 2014 Jul 18;79(14):6490-500. doi: 10.1021/jo500902n. Epub 2014 Jun 26.
We report herein a new strategy of the Rh(III)-catalyzed C-H activation/cyclization of indoles and pyrroles, for the divergent synthesis of privileged heterocycles. A simple derivation of indoles and pyrroles to N-carboxamides with oxidative bidentate directing group could enable rhodacycle formation and late-stage redox-neutral cyclization with alkynes, alkenes and diazo compounds, for access to five- and six-membered fused heterocycles, such as pyrimido[1,6-a]indol-1(2H)-one, 3,4-dihydropyrimido[1,6-a]indol-1(2H)-one, and 1H-imidazo[1,5-a]indol-3(2H)-ones. Kinetic isotope effect study was conducted, and a plausible mechanism was proposed. Furthermore, this protocol was applied to concise synthesis of 5-HT3 receptor antagonist in gram-scale.
我们在此报告一种铑（III）催化吲哚和吡咯的C-H活化/环化反应的新策略，用于多样化合成具有特殊结构的杂环化合物。通过简单地将吲哚和吡咯衍生为带有氧化双齿导向基团的N-羧酰胺，能够实现铑环的形成以及与炔烃、烯烃和重氮化合物的后期氧化还原中性环化反应，从而得到五元及六元稠合杂环化合物，如嘧啶并[1,6-a]吲哚-1(2H)-酮、3,4-二氢嘧啶并[1,6-a]吲哚-1(2H)-酮和1H-咪唑并[1,5-a]吲哚-3(2H)-酮。进行了动力学同位素效应研究，并提出了一个合理的反应机理。此外，该方法还被应用于克级规模的5-HT3受体拮抗剂的简洁合成。
