Synlett 2015; 26(16): 2296-2300
DOI: 10.1055/s-0035-1560091
letter
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Tandem Approach to 3-(Diarylmethylene)oxindoles Using Microwave Irradiation

Sunhwa Park
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea   Email: jaehongseo@catholic.ac.kr
,
Kye Jung Shin
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea   Email: jaehongseo@catholic.ac.kr
,
Jae Hong Seo*
Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea   Email: jaehongseo@catholic.ac.kr
› Author Affiliations
Further Information

Publication History

Received: 14 June 2015

Accepted after revision: 10 July 2015

Publication Date:
12 August 2015 (online)


Abstract

We developed a rapid and efficient microwave-assisted tandem reaction for the synthesis of 3-(diarylmethylene)oxindoles. Three palladium-catalyzed reactions (Sonogashira, Heck, and Suzuki–Miyaura reactions) were combined under microwave irradiation conditions to produce 3-(diarylmethylene)oxindoles from simple propiolamides, aryl iodides, and arylboronic acids. The addition of Ag3PO4 enhanced the yield and stereoselectivity of the tandem reaction significantly.

Supporting Information

 
  • References and Notes

  • 3 Dong GR, Park S, Lee D, Shin KJ, Seo JH. Synlett 2013; 24: 1993
  • 4 Yu L.-F, Li Y.-Y, Su M.-B, Zhang M, Zhang W, Zhang L.-N, Pang T, Zhang R.-T, Liu B, Li J.-Y, Li J, Nan F.-J. ACS Med. Chem. Lett. 2013; 4: 475
  • 6 According to unpublished results from our group, Ag3PO4 is a better silver salt additive for the reaction than AgOTf, which was used in previous work (see ref. 3).
  • 10 Palladium-Catalyzed Tandem Reaction under Microwave Irradiation; General Procedure: A microwave reaction vial was charged with N-methylpropiolamide (0.5 mmol, 1.0 equiv), aryl iodide (0.55 mmol, 1.1 equiv), aryl boronic acid (0.65 mmol, 1.3 equiv), CuI (0.025 mmol, 5 mol%), NaOAc (1.5 mmol, 3.0 equiv), Pd(PPh3)4 (0.05 mmol, 10 mol%), Ag3PO4 (0.55 mmol, 1.1 equiv), and DMF (5 mL). The reaction vial was sealed and exposed to microwave irradiation conditions for the indicated time and temperature. The mixture was cooled to 25 °C and diluted with EtOAc (200 mL). The organic layer was washed with H2O (3 × 30 mL) and brine (30 mL), then dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography (silica gel; hexane–EtOAc) to give 3-(diarylmethylene)oxindoles 6 and 9. (Z)-3-[(3-Methoxyphenyl)(phenyl)methylene]-1-methylindolin-2-one [(Z)-9k]: Yellow solid; mp 118.2 °C; Rf = 0.21 (silica gel; hexanes–EtOAc, 4:1). IR (film): 3535, 3055, 2927, 2214, 1700, 1604, 1096, 734 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.43–7.41 (m, 3 H), 7.33–7.29 (m, 3 H), 7.15 (td, J = 7.7, 1.0 Hz, 1 H), 6.95 (d, J = 7.8 Hz, 1 H), 6.91 (dd, J = 8.3, 1.9 Hz, 1 H), 6.83 (t, J = 1.9 Hz, 1 H), 6.76 (d, J = 7.8 Hz, 1 H), 6.66 (td, J = 7.7, 1.0 Hz, 1 H), 6.42 (d, J = 7.6 Hz, 1 H), 3.76 (s, 3 H), 3.20 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 166.8, 159.3, 154.3, 143.5, 141.5, 141.3, 129.3, 129.3, 129.1, 128.9, 128.9, 124.5, 123.3, 122.5, 121.5, 115.7, 114.4, 107.8, 55.4, 26.0. HRMS (EI): m/z calcd for C23H19NO2: 341.1416; found: 341.1422. (E)-3-[(3-Methoxyphenyl)(phenyl)methylene]-1-methylindolin-2-one [(E)-9k]: Yellow solid; mp 53.0 °C; Rf = 0.26 (silica gel; hexanes–EtOAc, 4:1). IR (film): 3287, 3055, 2937, 1700, 1604, 1469, 1094, 698 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.37–7.33 (m, 6 H), 7.16 (td, J = 7.7, 1.1 Hz, 1 H), 6.98 (ddd, J = 8.3, 2.6, 0.9 Hz, 1 H), 6.77 (dt, J = 9.9, 1.9 Hz, 1 H), 6.84 (dd, J = 2.5, 1.6 Hz, 1 H), 6.76 (d, J = 7.8 Hz, 1 H), 6.69 (td, J = 7.7, 1.0 Hz, 1 H), 6.48 (d, J = 7.3 Hz, 1 H), 3.77 (s, 3 H), 3.20 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 166.9, 160.1, 154.4, 143.5, 142.7, 139.9, 130.2, 130.0, 129.2, 128.9, 128.0, 124.4, 123.5, 123.3, 121.7, 121.6, 115.0, 114.5, 107.8, 55.5, 26.0. HRMS (EI): m/z [M+] calcd for C23H19NO2: 341.1416; found 341.1417.