Department of Chemical Sciences, Tezpur University, Napaam, Sonitpur, Assam 784028, India.
J Org Chem. 2023 Jul 7;88(13):9237-9248. doi: 10.1021/acs.joc.3c00813. Epub 2023 Jun 8.
Base-mediated [4+2] annulation of indole-2-carboxamides with 2,3-epoxy tosylates has been explored. The protocol delivers 3-substituted pyrazino[1,2-]indol-1-ones in high yields in diastereoselective fashion, and neither 4-substituted pyrazino[1,2-]indol-1-ones nor tetrahydro-1-[1,4]diazepino[1,2-]indol-1-ones are generated, irrespective of whether the distal epoxide C3 substituent is alkyl or aryl, or the epoxide is - or -configured. This reaction proceeds in one pot via N-alkylation of the indole scaffold with 2,3-epoxy tosylates, concomitantly followed by 6-exo-selective epoxide-opening cyclization. Notably, the process is chemo- and regioselective with respect to both the starting materials. To our knowledge, the process represents the first successful example of one-pot annulation of indole-based diheteronucleophiles with epoxide-based dielectrophiles.
已探索了吲哚-2-甲酰胺与 2,3-环氧对甲苯磺酸酯的基于碱基的 [4+2] 环加成反应。该方案以高非对映选择性方式提供了 3-取代的吡嗪并[1,2-]吲哚-1-酮，并且无论远端环氧化物 C3 取代基是烷基还是芳基，或者环氧化物是 - 或 - 构型，都不会生成 4-取代的吡嗪并[1,2-]吲哚-1-酮或四氢-1-[1,4]二氮杂并[1,2-]吲哚-1-酮。该反应通过 2,3-环氧对甲苯磺酸酯与吲哚骨架的 N-烷基化在一锅法中进行，同时随后进行 6-endo-选择性环氧化物开环环化。值得注意的是，该过程在起始原料方面具有化学和区域选择性。据我们所知，该过程代表了基于吲哚的双杂亲核试剂与基于环氧化物的双亲电试剂一锅法环加成的首例成功实例。
