Nambu Hisanori, Hirota Wataru, Fukumoto Masahiro, Tamura Takafumi, Yakura Takayuki
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, 930-0194, Japan.
Chemistry. 2017 Nov 27;23(66):16799-16805. doi: 10.1002/chem.201702622. Epub 2017 Sep 5.
An efficient route to highly substituted indoles was developed. It included regioselective functionalization of tetrahydroindol-4(5H)-ones, prepared by ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines, and subsequent oxidation. The 6-substituted indoles were synthesized from a readily available 5-substituted cyclohexane-1,3-dione-2-spirocyclopropane. The synthesis of 5- and 7-substituted indoles was achieved by regioselective electrophilic alkylation of tetrahydroindol-4(5H)-one, followed by oxidation. The 4-substituted indoles were synthesized by nucleophilic alkylation of the corresponding pyrrole derivative, which was prepared by partial oxidation of tetrahydroindol-4(5H)-one, and sequential oxidation. The synthesis of 4-substituted indoles was also accomplished by palladium-catalyzed coupling of 4-hydroxyindole-derived triflates. Furthermore, the synthesis of 4,5,6,7-tetrasubstituted indoles was achieved by using these regioselective alkylations.
开发了一条通往高度取代吲哚的有效路线。它包括对四氢吲哚 -4(5H)- 酮进行区域选择性官能化，该四氢吲哚 -4(5H)- 酮是通过环己烷 -1,3- 二酮 -2- 螺环丙烷与伯胺的开环环化反应制备的，随后进行氧化。6- 取代吲哚由易于获得的 5- 取代环己烷 -1,3- 二酮 -2- 螺环丙烷合成。5- 和 7- 取代吲哚的合成是通过四氢吲哚 -4(5H)- 酮的区域选择性亲电烷基化反应，然后氧化来实现的。4- 取代吲哚是通过相应吡咯衍生物的亲核烷基化反应合成的，该吡咯衍生物是通过四氢吲哚 -4(5H)- 酮的部分氧化制备的，然后依次氧化。4- 取代吲哚的合成也通过钯催化的 4- 羟基吲哚衍生的三氟甲磺酸酯的偶联反应完成。此外，通过使用这些区域选择性烷基化反应实现了 4,5,6,7- 四取代吲哚的合成。
