Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime
In this paper, we report the synthesis of spirocyclopropane-containing 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indoles <b>6a</b>–<b>e</b> via alkylative dearomatization and intramolecular <i>N</i>-imination of indole–<i>O</i>-(methylsul...
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MDPI AG
2023-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/17/6374 |
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| author | Jiann-Jyh Huang Hung-Chun Liao Cheng-En Hsu Yan-Ru Liu Yi-Fu Chang Shan-Yen Chou |
| author_facet | Jiann-Jyh Huang Hung-Chun Liao Cheng-En Hsu Yan-Ru Liu Yi-Fu Chang Shan-Yen Chou |
| author_sort | Jiann-Jyh Huang |
| collection | DOAJ |
| description | In this paper, we report the synthesis of spirocyclopropane-containing 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indoles <b>6a</b>–<b>e</b> via alkylative dearomatization and intramolecular <i>N</i>-imination of indole–<i>O</i>-(methylsulfonyl)oxime <b>11</b>. Starting materials tryptophol (<b>7</b>) and 2-bromocyclopetanone (<b>8</b>) were reacted in the presence of HBF<sub>4</sub>·OEt<sub>2</sub>, providing 1,2,3,5,6,11-hexahydrocyclopenta[2,3]oxepino[4,5-<i>b</i>]indole (<b>9</b>) in a 63% yield. Compound <b>9</b> was reacted with hydroxylamine hydrochloride to afford oxime <b>10</b> (65% yield), which was subsequently bis-methanesulfonated to form <b>11</b> in a 85% yield. Heating <b>11</b> with various alcohols in the presence of <i>N</i>,<i>N</i>-diisopropylethylamine (DIPEA) triggered the alkylative dearomatization and intramolecular <i>N</i>-imination, forming the spirocyclopropane and 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indole structures in the targets <b>6a</b>–<b>e</b> with 67–84% yields. |
| first_indexed | 2024-03-10T23:16:50Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T23:16:50Z |
| publishDate | 2023-08-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e47f2638374949dabf64dbc4fe5800762023-11-19T08:35:05ZengMDPI AGMolecules1420-30492023-08-012817637410.3390/molecules28176374Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oximeJiann-Jyh Huang0Hung-Chun Liao1Cheng-En Hsu2Yan-Ru Liu3Yi-Fu Chang4Shan-Yen Chou5Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDepartment of Applied Chemistry, National Chiayi University, Chiayi City 600, TaiwanDepartment of Applied Chemistry, National Chiayi University, Chiayi City 600, TaiwanDepartment of Applied Chemistry, National Chiayi University, Chiayi City 600, TaiwanDepartment of Applied Chemistry, National Chiayi University, Chiayi City 600, TaiwanDevelopment Center for Biotechnology, National Biotechnology Research Park, Taipei City 115, TaiwanIn this paper, we report the synthesis of spirocyclopropane-containing 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indoles <b>6a</b>–<b>e</b> via alkylative dearomatization and intramolecular <i>N</i>-imination of indole–<i>O</i>-(methylsulfonyl)oxime <b>11</b>. Starting materials tryptophol (<b>7</b>) and 2-bromocyclopetanone (<b>8</b>) were reacted in the presence of HBF<sub>4</sub>·OEt<sub>2</sub>, providing 1,2,3,5,6,11-hexahydrocyclopenta[2,3]oxepino[4,5-<i>b</i>]indole (<b>9</b>) in a 63% yield. Compound <b>9</b> was reacted with hydroxylamine hydrochloride to afford oxime <b>10</b> (65% yield), which was subsequently bis-methanesulfonated to form <b>11</b> in a 85% yield. Heating <b>11</b> with various alcohols in the presence of <i>N</i>,<i>N</i>-diisopropylethylamine (DIPEA) triggered the alkylative dearomatization and intramolecular <i>N</i>-imination, forming the spirocyclopropane and 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indole structures in the targets <b>6a</b>–<b>e</b> with 67–84% yields.https://www.mdpi.com/1420-3049/28/17/63744<i>H</i>-pyrazolo[1,5-<i>a</i>]indolepyrazoloindolespirocyclopropanealkylative dearomatization<i>N</i>-iminationindole |
| spellingShingle | Jiann-Jyh Huang Hung-Chun Liao Cheng-En Hsu Yan-Ru Liu Yi-Fu Chang Shan-Yen Chou Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime Molecules 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indole pyrazoloindole spirocyclopropane alkylative dearomatization <i>N</i>-imination indole |
| title | Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime |
| title_full | Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime |
| title_fullStr | Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime |
| title_full_unstemmed | Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime |
| title_short | Synthesis of Spirocyclopropane-Containing 4<i>H</i>-Pyrazolo[1,5-<i>a</i>]indoles via Alkylative Dearomatization and Intramolecular <i>N</i>-Imination of an Indole–<i>O</i>-(Methylsulfonyl)oxime |
| title_sort | synthesis of spirocyclopropane containing 4 i h i pyrazolo 1 5 i a i indoles via alkylative dearomatization and intramolecular i n i imination of an indole i o i methylsulfonyl oxime |
| topic | 4<i>H</i>-pyrazolo[1,5-<i>a</i>]indole pyrazoloindole spirocyclopropane alkylative dearomatization <i>N</i>-imination indole |
| url | https://www.mdpi.com/1420-3049/28/17/6374 |
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