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Synlett 2013; 24(14): 1856-1860
DOI: 10.1055/s-0033-1339449
letter
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Intramolecular Cyclization of 2-Iodobenzamides: ­An Efficient Synthesis of 3-Acyl Isoindolin-1-ones and 3-Hydroxy-3-acyliso­indolin-1-ones

Wanli Chen*
a   Center of Analysis & Measurement, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Fax: +86(571)88320961   Email: chenwl@zjut.edu.cn
,
Lina Jin
a   Center of Analysis & Measurement, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Fax: +86(571)88320961   Email: chenwl@zjut.edu.cn
,
Yinghong Zhu*
b   College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: yhzhuchem@zjut.edu.cn
,
Xiaoji Cao
a   Center of Analysis & Measurement, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Fax: +86(571)88320961   Email: chenwl@zjut.edu.cn
,
Lebin Zheng
a   Center of Analysis & Measurement, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Fax: +86(571)88320961   Email: chenwl@zjut.edu.cn
,
Weimin Mo
a   Center of Analysis & Measurement, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Fax: +86(571)88320961   Email: chenwl@zjut.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 23 April 2013

Accepted after revision: 20 June 2013

Publication Date:
24 July 2013 (online)

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Abstract

Palladium-catalyzed intramolecular cyclization of 2-iodo­benzamides with a 2-oxoethyl function group on the nitrogen atom moiety is presented, providing an efficient method for the synthesis of 3-acyl isoindolin-1-ones and 3-hydroxy-3-acylisoindolin-1-ones under mild conditions in moderate yields.

Key words

intramolecular cyclization - palladium-catalyzed - 3-acyl isoindolin-1-ones - 3-hydroxy-3-acylisoindolin-1-ones - ­2-iodobenzamides

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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  • 20 General Procedure for the Synthesis of 2:2-Iodobenzamide 1 (0.3 mmol), Pd2(dba)3·CHCl3 (0.0075 mmol), Xantphos (0.015 mmol), and i-PrOH (1 mL) were added into a Schlenk tube at r.t. under N2. After stirring for 5 min, Et3N (1 mL) was added. The reaction mixture was stirred at 70 °C until the reaction was complete, as monitored by TLC (usually 2–5 h). Then the reaction mixture was cooled and the solvent was removed under reduced pressure. Dilute HCl (15 mL) was added, the aqueous layer was extracted with EtOAc (3 × 15 mL) and dried over MgSO4. After filtration and removal of the solvent in vacuo, the residues were purified by flash chromatography (silica gel; PE–EtOAc, 5:1 → 4:1) to afford 2.3-Benzoyl-2-phenylisoindolin-1-one (2a): solid (mp 178–180 °C). 1H NMR (500 MHz, CDCl3): δ = 7.99 (d, J = 7.4 Hz, 1 H), 7.95 (d, J = 7.5 Hz, 2 H), 7.69 (d, J = 8.0 Hz, 2 H), 7.64 (t, J = 7.5 Hz, 1 H), 7.47–7.54 (m, 4 H), 7.33 (t, J = 8.2 Hz, 2 H), 7.29 (d, J = 7.5 Hz, 1 H), 7.13 (d, J = 7.4 Hz, 1 H), 6.65 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 193.3, 167.7, 138.8, 138.1, 135.1, 134.2, 132.4, 132.3, 129.4, 129.2, 129.1, 128.7, 125.1, 124.8, 122.5, 121.0, 67.0. IR: 3056, 1687, 1372, 752 cm–1. HRMS (ESI): m/z [M + H]+ calcd for C21H16NO2: 314.1181; found: 314.1177.
  • 22 General Procedure for the Synthesis of 3:2-Iodobenzamides 1 (0.3 mmol), Pd2(dba)3·CHCl3 (0.0075 mmol), Xantphos (0.015 mmol), and i-PrOH (1 mL) were added into a Schlenk tube at r.t. under N2. After stirring for 5 min, Et3N (1 mL) was added. The reaction mixture was stirred at 70 °C until the reaction was complete, as monitored by TLC (usually 2–5 h). Then the reaction mixture was stirred continuously under O2 for 24 h. The reaction mixture was cooled and the solvent was removed under reduced pressure. Saturated NaCl (15 mL) was added, the aqueous layer was extracted with EtOAc (3 × 15 mL) and dried over MgSO4. After filtration and removal of the solvent in vacuo, the residues were purified by flash chromatography (silica gel; PE–EtOAc, 5:1 → 4:1) to afford 3.3-Benzoyl-3-hydroxy-2-phenylisoindolin-1-one (3a): solid (mp 124–126 °C). 1H NMR (500 MHz, CDCl3): δ = 8.05–8.07 (m, 1 H), 7.61–7.67 (m, 2 H), 7.47–7.51 (m, 3 H), 7.40–7.41 (m, 1 H), 7.24–7.29 (m, 5 H), 7.19–7.21 (m, 2 H), 6.02 (br s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 195.7, 167.8, 144.1, 134.7, 134.2, 133.6, 132.4, 131.4, 130.8, 129.3, 129.0, 128.8, 127.6, 126.8, 124.8, 122.7, 91.8. IR: 3254, 1684, 1386, 741 cm–1. HRMS (ESI): m/z [M + H]+ calcd for C21H16NO3: 330.1130; found: 330.1142.