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Synlett 2023; 34(12): 1457-1461
DOI: 10.1055/a-2043-4862
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Special Issue Honoring Masahiro Murakami’s Contributions to Science

Facile Synthesis of Isoindolinones via Radical-Mediated Intramolecular Coupling of Two C–H Bonds

Shuxiong Han
a   Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. of China
,
Shuo He
a   Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. of China
,
Zhibin Huang
a   Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. of China
,
Yingsheng Zhao∗
a   Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. of China
,
Gong Chen∗
b   State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, P. R. of China
› Author AffiliationsThis work was supported by National Natural Science Foundation of China (No. 22171197), the Major Basic Research Project of the Natural Science Foundation of Jiangsu Higher Education Institutions (21KJA150002), National Local Joint Engineering Laboratory to Functional Adsorption Material Technology for the Environmental Protection (SDGC2121) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) project. The project was also supported by the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University.
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Abstract

A metal-free method for the construction of 3,3-dimethyl isoindolinones via radical-mediated intramolecular coupling of two C–H bonds of N,N-diisopropyl benzamides was developed. The reactions can proceed in moderate to high yield and with excellent chemoselectivity. A reaction sequence of the formation of an alkyl radical via oxidative cleavage of alkyl C–H bond and the formation of lactam ring via intramolecular homolytic aromatic substitution was proposed.

Key words

C–H activation - isoindolinone - homolytic aromatic substitution - alkyl radical - benzamide

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2043-4862.
  • Supporting Information


Publication History

Received: 15 January 2023

Accepted after revision: 27 February 2023

Accepted Manuscript online:
27 February 2023

Article published online:
17 March 2023

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  • 15 Representative Procedure for Isoindolone Synthesis The mixture of benzamide 1a (41.0 mg, 0.2 mmol), (NH4)2S2O8 (91.3 mg, 0.4 mmol), AcOH (34.4 μL, 0.6 mmol), and MeCN (1.0 mL) was sealed in a 15 mL glass vial under Ar with a ground-glass-type stopper. The reaction mixture was then stirred at 120 °C for 12 h before cooling to room temperature and being concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate: 10/1 to 5/1) to give the isoindolinone product 2a as a white solid (27.2 mg, 68%). 1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 7.5 Hz, 1 H, ArH), 7.52–7.48 (m, 1 H, ArH), 7.42–7.38 (m, 1 H, ArH), 7.34 (d, J = 7.5 Hz, 1 H, ArH), 3.70–3.60 (m, 1 H, CH), 1.56 (d, J = 6.9 Hz, 6 H, CH3), 1.48 (s, 6 H, CH3). 13C NMR (100 MHz, CDCl3): δ = 167.4, 151.4, 132.1, 131.4, 128.0, 123.4, 120.7, 63.4, 44.7, 25.6, 20.6. HRMS: m/z calcd for C13H17NNaO [M + Na]+: 226.1202; found: 226.1207.
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