Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226001, India.
J Org Chem. 2013 Sep 6;78(17):8624-33. doi: 10.1021/jo4013332. Epub 2013 Aug 14.
A two-step protocol for the diversity-oriented synthesis of annulated indoles following MCR-post MCR modification concept is described. The reaction initially proceeds through the annulation of 2-(2,2-dibromovinyl)aniline, an isocyanate, and a terminal alkyne in a three-component tandem format via Cu/Pd-catalyzed cross coupling to afford N-1 and C-2 functionalized indole. In the subsequent step, the enyne-urea derivative undergoes chemo- and regioselective 6-endo cyclization to afford O-cyclized product in the presence of Au(I)/AgNO3 and N-cyclized product in the presence of Au(I)/AgOTf under a post-MCR modification step. A mechanistic investigation following a recent pioneering work on the silver effect in gold catalysis (Shi, X. J. Am. Chem. Soc. 2012, 134, 9012) explains the role of counterion on Au/Ag-catalyzed regiodivergent pathways.
描述了一种两步策略，用于通过 MCR 后 MCR 修饰概念，实现稠合吲哚的多样性导向合成。该反应最初通过铜/钯催化的交叉偶联，在三组分串联格式中，通过 2-(2,2-二溴乙烯基)苯胺、异氰酸酯和末端炔烃的环化反应，得到 N-1 和 C-2 官能化的吲哚。在随后的步骤中，在金（I）/AgNO3 存在下，烯炔脲衍生物发生化学和区域选择性的 6-endo 环化，在 MCR 后修饰步骤中，在金（I）/AgOTf 存在下，发生 O-环化产物；在金催化中银的作用的最新开创性工作（Shi, X. J. Am. Chem. Soc. 2012, 134, 9012）之后进行了机理研究，解释了抗衡离子在 Au/Ag 催化的区域发散途径中的作用。
