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Synthesis of Indene[1,2-c] isoquinoline-11-one by Rhodium-catalyzed Benzimide-directed C-H Activation

文献类型：期刊论文

作者Huang Jiaxin1,3; Liu Min3; Xu Hui3; Dai Hui-Xiong1,2,3
刊名ACTA CHIMICA SINICA
出版日期2024-06-15
卷号82期号:6页码:565-569
关键词indene[1,2-c]isoquinoline C-H activation rhodium catalyst
ISSN号0567-7351
DOI10.6023/A24040136
通讯作者Dai Hui-Xiong(hxdai@simm.ac.cn)
英文摘要Indene[1,2-c]isoquinoline is a novel non-camptothecin-like Topo1 inhibitor, and possesses good antitumour effect on lung cancer, lymphoma, etc. Thus, the development of new methodologies to construct indene[1,2-c]isoquinoline and its derivatives has been a hot topic in organic chemistry. In recent years, benzimidate has been widely used as a building block in the construction of nitrogen-containing heterocycles via transition metal-catalyzed C(sp(2))-H bond activation and subsequent cyclization reaction with different reagents, such as alkyne, alkene, carbenes. Meanwhile, alpha-diazo carbonyl compounds have been widely used as C2 synthons in organic synthesis. In particular, with cyclic alpha-diazo-1,3-diketones, fused polycyclic compounds could also be prepared via Rh(III)-catalyzed [4+2] oxidative annulations. Herein, we report the construction of indene[1,2-c]isoquinoline-11-one using benzimidate and alpha-diazo carbonyl compounds as the starting material. The reaction proceeds via a rhodium-catalyzed C-H activation/carbenoid insertion/dehydration process. The protocol showed high atom economy, excellent functional group tolerance, and heterocycle compatibility, giving the indene[1,2-c]isoquinoline-11-one in moderate-to-good yields. Wolff-Kishner reduction of the product with N2H4 center dot H2O affords the indene[1,2-c]isoquinoline. To demonstrate the synthetic utility of this protocol, gram-scale synthesis and late-stage modification of drug molecule were showcased. The KIE value of 3.4:1 indicated that the C-H cleavage step is probably involved in the rate-determined step. A typical general procedure for the synthesis of indene[1,2-c]isoquinoline-11-one 3a is described as the following: To a solution of ethyl benzimidate (0.1 mmol), [Cp*RhCl2](2) (1.5 mg, 2.5 mol%), and AgOAc (3.2 mg, 20 mol%) in hexafluoroisopropanol (2 mL) was added diazooxindole (0.11 mmol) under N2. The mixture was stirred at 100. for 12 h. Then the reaction mixture was cooled to room temperature. The mixture was filtered through Celite, and the filtrate was evaporated to give the crude product which was then purified by flash column chromatography on silica gel with a gradient eluent of petroleum ether/ethyl acetate (V/V, 10/1) to give the product 3a.
WOS关键词ANNULATION ; DERIVATIVES ; TRANSITION ; EFFICIENT ; COMPLEX ; ACCESS
资助项目National Natural Science Foundation of China[22171276] ; National Natural Science Foundation of China[21920102003] ; Science and Technology Commission of Shanghai Municipality[17JC1405000] ; Science and Technology Commission of Shanghai Municipality[21ZR1475400] ; Science and Technology Commission of Shanghai Municipality[23ZR1474400] ; 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
WOS记录号WOS:001282008300001
出版者SCIENCE PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/313050]  
专题新药研究国家重点实验室
通讯作者Dai Hui-Xiong
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Organomet Chem, Shanghai 200032, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Huang Jiaxin,Liu Min,Xu Hui,et al. Synthesis of Indene[1,2-c] isoquinoline-11-one by Rhodium-catalyzed Benzimide-directed C-H Activation[J]. ACTA CHIMICA SINICA,2024,82(6):565-569.
APA Huang Jiaxin,Liu Min,Xu Hui,&Dai Hui-Xiong.(2024).Synthesis of Indene[1,2-c] isoquinoline-11-one by Rhodium-catalyzed Benzimide-directed C-H Activation.ACTA CHIMICA SINICA,82(6),565-569.
MLA Huang Jiaxin,et al."Synthesis of Indene[1,2-c] isoquinoline-11-one by Rhodium-catalyzed Benzimide-directed C-H Activation".ACTA CHIMICA SINICA 82.6(2024):565-569.

入库方式： OAI收割

来源：上海药物研究所

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