Construction of Aza-spiro[4,5]indole Scaffolds via Rhodium-Catalyzed Regioselective C(4)-H Activation of Indole
文献类型：期刊论文
| 作者 | Wang Mengmeng2; Zhang Jun1; Wang Huiying2; Ma Biao1; Dai Hui-Xiong1,2,3
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| 刊名 | ACTA CHIMICA SINICA
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| 出版日期 | 2022-03-15 |
| 卷号 | 80期号:3页码:277-281 |
| ISSN号 | 0567-7351 |
| 关键词 | indole spirocycle C-H activation Rh-catalyst |
| DOI | 10.6023/A21120588 |
| 通讯作者 | Ma Biao(bma@simm.ac.cn) ; Dai Hui-Xiong(hxdai@simm.ac.cn) |
| 英文摘要 | Indole skeletons are widely used in drug research and development as a "privileged structure", while spirocyclic scaffold as a common structural unit, usually plays an important role in the bioactivity and physicochemical properties of molecule skeletons. Hence, spiroindoles which incorporate both indole and spirocycle units have great significance and widespread applications in pharmaceutical field, and substantial progress has been made in the field for their construction and modification. C-H Activation via directing group's assistance has emerged as a powerful approach in the field of organic synthesis. To date, various 2- and 3-indolyl-tethered aza-spiro-centres via C-H activation have been successfully achieved. However, due to the inherent reactivity of the pyrrole side of the indole, introduction of spiro-containing systems onto the benzenoid core of indole still remains challenging. Here, by installing an appropriate directing group onto the C(3) position of indole, a mild and efficient method of Rh011)-catalyzed selectively C(4)-H activation/cyclization of indole with diazo compound was developed. As a result, a series of novel aza-spiro[4,5]indole derivatives were obtained in mild to excellent yields. The protocol showed excellent functional group tolerance. Gram-scale synthesis demonstrated the utility of this protocol, and further modification via click chemistry offered the novel scaffold as a versatile spiro linker. A general procedure for the synthesis of spiroindole derivatives is described as the following: to a solution of N-(pivaloyloxy)-indol-e3-carboxamide (0.1 mmol), [Cp*RhCl2](2) (1.6 mg, 2.5 mol%) and NaOAc (1.6 mg, 20 mol%) in CH3CN (1 mL) was added diazooxindole (0.12 mmol) under air. Then the reaction mixture was stirred at room temperature for 12 h. After completion of the reaction, the resulting mixture was diluted with 25 mL of EtOAc, and filtered through a celite pad. Then the filtrate was concentrated under vacuum to give the crude product, which was purified via silica gel to obtain the corresponding spiroindole product. |
| WOS关键词 | DIRECTING GROUP ; FUNCTIONALIZATION ; ALKYLATION ; TRYPTOPHAN ; ALKALOIDS ; C4 |
| 资助项目 | National Natural Science Foundation of China[22001258] ; National Natural Science Foundation of China[21920102003] ; Youth Innovation Promotion Association CAS[2018293] ; Science and Technology Commission of Shanghai Municipality[17JC1405000] ; Science and Technology Commission of Shanghai Municipality[21ZR1475400] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; Program of Shanghai Academic Research Leader[19XD1424600] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| 出版者 | SCIENCE PRESS |
| WOS记录号 | WOS:000779370500008 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299869]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Ma Biao; Dai Hui-Xiong |
| 作者单位 | 1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 3.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang Mengmeng,Zhang Jun,Wang Huiying,et al. Construction of Aza-spiro[4,5]indole Scaffolds via Rhodium-Catalyzed Regioselective C(4)-H Activation of Indole[J]. ACTA CHIMICA SINICA,2022,80(3):277-281. |
| APA | Wang Mengmeng,Zhang Jun,Wang Huiying,Ma Biao,&Dai Hui-Xiong.(2022).Construction of Aza-spiro[4,5]indole Scaffolds via Rhodium-Catalyzed Regioselective C(4)-H Activation of Indole.ACTA CHIMICA SINICA,80(3),277-281. |
| MLA | Wang Mengmeng,et al."Construction of Aza-spiro[4,5]indole Scaffolds via Rhodium-Catalyzed Regioselective C(4)-H Activation of Indole".ACTA CHIMICA SINICA 80.3(2022):277-281. |
入库方式： OAI收割
来源：上海药物研究所
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