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Synlett 2016; 27(12): 1848-1853
DOI: 10.1055/s-0035-1561859
letter
© Georg Thieme Verlag Stuttgart · New York

Novel Methodology for the Efficient Synthesis of 3-Aryloxindoles: [1,2]-Phospha-Brook Rearrangement–Palladium-Catalyzed Cross-Coupling Sequence

Azusa Kondoh
a   Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan   Email: mterada@m.tohoku.ac.jp
,
Akira Takei
b   Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan
,
Masahiro Terada*
a   Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan   Email: mterada@m.tohoku.ac.jp
b   Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan
› Author Affiliations
Further Information

Publication History

Received: 07 March 2016

Accepted after revision: 30 March 2016

Publication Date:
07 April 2016 (online)

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Abstract

A novel methodology for the efficient synthesis of 3-aryloxindoles from isatin derivatives was developed. The methodology involves the formation of an oxindole having a phosphate moiety at the C-3 position via the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis followed by palladium-catalyzed cross-coupling with aryl boron reagents. The one-pot synthesis of 3-aryloxindoles from isatin derivatives is also described.

Key words

oxindole derivatives - phospha-Brook rearrangement - Brønsted base catalysis - cross-coupling - palladium catalyst

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561859.
  • Supporting Information
 

  • References and Notes

  • 3 Bruce JM, Sutcliffe FK. J. Chem. Soc. 1957; 4789
    Crossref
  • 4 Fleming I, Loreto MA, Wallace IH. M, Michael JP. J. Chem. Soc., Perkin Trans. 1 1986; 349
    Crossref
  • 13 Typical Procedure for the Synthesis of Oxindole Derivatives 2 Synthesis of 2a is representative. To a solution of 1a (1.0 g, 4.3 mmol) and diphenyl phosphite (0.92 mL, 4.8 mmol) in toluene (8.7 mL) was added i-Pr2NEt (75 μL, 0.43 mmol). The resulting mixture was stirred at room temperature for 10 min. The reaction was quenched with sat. aq NH4Cl, and the product was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, and evaporated. The residue was purified by column chromatography (hexane–EtOAc, 2:1) to provide 2a (1.9 g, 4.1 mmol, 94%) as a colorless oil. Compound 2a: 1H NMR (600 MHz, CDCl3): δ = 1.08 (t, J = 7.2 Hz, 3 H), 3.63–3.95 (m, 2 H), 7.24–7.27 (m, 5 H), 7.28–7.31 (m, 1 H), 7.36–7.40 (m, 2 H), 7.52 (dd, J = 8.4, 1.2 Hz, 1 H), 7.54 (ddd, J = 7.2, 7.2, 1.2 Hz, 1 H), 7.59–7.62 (m, 1 H), 7.66 (ddd, J = 7.2, 7.2, 1.2 Hz, 1 H), 7.94 (dd, J = 7.8, 0.60 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 13.7, 62.0, 88.1, 93.6, 122.9, 123.2, 128.0, 128.16 (2 C), 128.23, 128.3, 130.0, 130.6, 131.2, 131.4, 132.2, 132.5, 134.7, 141.4, 141.7, 163.0, 188.5. 31P NMR (243 MHz, CDCl3): δ = –10.8. IR (ATR): 3061, 2984, 1748, 1731, 1691, 1597, 1496, 1442, 1197, 1020 cm–1. ESI-HRMS: m/z calcd for C24H18O3 [M + Na]+: 377.1148; found: 377.1148.
  • 15 Yamamoto Y, Takizawa M, Yu X.-Q, Miyaura N. Angew. Chem. Int. Ed. 2008; 47: 928
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  • 16 Typical Procedure for the Synthesis of 3-Aryloxindoles 4 The reaction of 2a and 3e is representative (Table 1, entry 18). Pd2(dba)3 (6.8 mg, 7.5 μmol) and XPhos (14 mg, 30 μmol) were dissolved in toluene (0.60 mL), and the solution was stirred for 15 min. Compound 2a (0.14 g, 0.30 mmol) in toluene (2.4 mL), NaHCO3 (50 mg, 0.60 mmol), 3e (0.11 g, 0.45 mmol), and H2O (1.5 mL) were sequentially added, and the resulting mixture was then warmed to 60 °C. After stirred for 7 h, the reaction was quenched with sat. aq NH4Cl, and the product was extracted with EtOAc. The combined organic layer was dried over Na2SO4 and evaporated. The crude mixture was purified by column chromatography (hexane–EtOAc, 4:1) to afford 4aa (72 mg, 0.24 mmol, 80%) as a white solid. Compound 4aa: 1H NMR (400 MHz, CDCl3): δ = 4.74 (s, 1 H), 4.90 (d, J = 15.6 Hz, 1 H), 5.00 (d, J = 15.6 Hz, 1 H), 6.79 (d, J = 7.8 Hz, 1 H), 7.02 (dd, J = 7.2, 7.2 Hz, 1 H), 7.14–7.18 (m, 1 H), 7.18–7.24 (m, 3 H), 7.24–7.37 (m, 8 H). 13C NMR (100 MHz, CDCl3): δ =  43.9, 52.0, 109.2, 122.7, 125.1, 127.3, 127.59, 127.62, 128.3, 128.4, 128.8, 128.89, 128.92, 135.9, 136.7, 143.6, 176.1.
  • 17 The exploratory investigation for reaction conditions are summarized in the Supporting Information.
  • 18 With these substrates 2, the reaction without NaHCO3 provided almost the same or slightly better yields than those obtained with NaHCO3.
  • 19 Procedure for the One-Pot Synthesis of 3-Aryloxindoles To a solution of 1a (50 mg, 0.21 mmol) and diphenyl phosphite (45 μL, 0.23 mmol) in toluene (0.42 mL) was added i-Pr2NEt (3.6 μL, 21 μmol). The resulting mixture was then stirred at room temperature for 10 min. A stock solution of Pd2(dba)3 (4.8 mg, 5.3 μmol) and XPhos (10 mg, 21 μmol) in toluene (0.42 mL), toluene (3.4 mL), NaHCO3 (35 mg, 0.42 mmol), 3e (77 mg, 0.31 mmol), and H2O (2.1 mL) were added sequentially, and the resulting mixture was then warmed to 60 °C. After stirred for 7 h, the reaction was quenched with sat. aq NH4Cl, and the product was extracted with EtOAc. The combined organic layer was dried over Na2SO4 and evaporated. The residue was purified by column chromatography (hexane–EtOAc, 4:1) to provide 4aa (43 mg, 0.14 mmol, 68%) as a white solid.