Synlett 2016; 27(12): 1794-1797
DOI: 10.1055/s-0035-1561658
letter
© Georg Thieme Verlag Stuttgart · New York

Zinc(II)-Assisted Aryl Finkelstein Reaction for the Synthesis of Aryl Iodides

Nico Ueberschaar
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Beutenbergstr. 11a, 07745, Jena, Germany   eMail: christian.hertweck@leibniz-hki.de
,
Daniel Heine
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Beutenbergstr. 11a, 07745, Jena, Germany   eMail: christian.hertweck@leibniz-hki.de
,
Christan Hertweck*
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Beutenbergstr. 11a, 07745, Jena, Germany   eMail: christian.hertweck@leibniz-hki.de
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Publikationsverlauf

Received: 20. November 2015

Accepted after revision: 03. Mai 2016

Publikationsdatum:
01. Juni 2016 (online)

Abstract

Aryl iodides play an important role in synthetic organic chemistry as they are frequently utilized in cross-coupling reactions and in oxidation processes using hypervalent iodine compounds. Their synthesis is, however, often cumbersome and may lead to unwanted side products. Here, we report on an improved protocol for the aryl Finkelstein reaction in which dehalogenation is prevented by addition of zinc iodide in lieu of copper(I). Generally, electron-poor ortho-bromo methyl benzoates, amides, and even unprotected phenols are well-suited for this method.

Supporting Information

 
  • References

  • 1 Brückner R. Reaktionsmechanismen: Organische Reaktionen, Stereochemie, Moderne Synthesemethoden. 3rd ed. Spektrum Akademischer Verlag; Heidelberg: 2009
  • 2 Silva JL. F, Olofsson B. Nat. Prod. Rep. 2011; 28: 1722
  • 3 Schwetlick K. Organikum. Vol. 21. Wiley-VCH; Weinheim: 2001
  • 4 Snieckus V. Chem. Rev. 1990; 90: 879
    • 5a Krasnokutskaya EA, Semenischeva NI, Filimonov VD, Knochel P. Synthesis 2007; 81
    • 5b Filimonov VD, Trusova M, Postnikov P, Krasnokutskaya EA, Lee YM, Hwang HY, Kim H, Chi KW. Org. Lett. 2008; 10: 3961
    • 5c Hodgson HH. Chem. Rev. 1947; 40: 251
  • 6 Cannon KA, Geuther ME, Kelly CK, Lin S, MacArthur AH. R. Organometallics 2011; 30: 4067
    • 7a Ma H, Li W, Wang J, Xiao G, Gong Y, Qi C, Feng Y, Li X, Bao Z, Cao W, Sun Q, Veaceslav C, Wang F, Lei Z. Tetrahedron 2012; 68: 8358
    • 7b Miles KC, Le CC, Stambuli JP. Chem. Eur. J. 2014; 20: 11336
    • 7c Reed NN, Delgado M, Hereford K, Clapham B, Janda KD. Bioorg. Med. Chem. 2002; 12: 2047
    • 7d Mülbaier M, Giannis A. Angew. Chem. Int. Ed. 2001; 40: 4393
  • 8 Limpricht H. Liebigs Ann. Chem. 1891; 263: 224
  • 9 Datta RL, Prosad N. J. Am. Chem. Soc. 1917; 39: 441
    • 10a Ueberschaar N, Dahse H.-M, Bretschneider T, Hertweck C. Angew. Chem. Int. Ed. 2013; 52: 6185
    • 10b Ueberschaar N, Xu Z, Scherlach K, Metsä-Ketelä M, Bretschneider T, Dahse H.-M, Goerls H, Hertweck C. J. Am. Chem. Soc. 2013; 135: 17408
  • 11 Cant AA, Bhalla R, Pimlott SL, Sutherland A. Chem. Commun. 2012; 48: 3993
  • 12 Imazaki Y, Shirakawa E, Ueno R, Hayashi T. J. Am. Chem. Soc. 2012; 134: 14760
  • 13 Li L, Liu W, Zeng H, Mu X, Cosa G, Mi Z, Li C.-J. J. Am. Chem. Soc. 2015; 137: 8328
  • 14 Sejberg JJ. P, Smith LD, Leatherbarrow RJ, Beavil AJ, Spivey AC. Tetrahedron Lett. 2013; 54: 4970
  • 15 Bennacef I, Haile CN, Schmidt A, Koren AO, Seibyl JP, Staley JK, Bois F, Baldwin RM, Tamagnan G. Bioorg. Med. Chem. 2006; 14: 7582
  • 16 Hapke M, Kral K, Spannenberg A. Synthesis 2011; 642
  • 17 Hekmatshoar R, Sajadi S, Heravi MM. J. Chin. Chem. Soc. 2008; 55: 616
    • 18a Sheppard TD. Org. Biomol. Chem. 2009; 7: 1043
    • 18b Klapars A, Buchwald SL. J. Am. Chem. Soc. 2002; 124: 14844
    • 19a All reagents were obtained from commercial suppliers and used without further purification unless otherwise stated. All solvents used were spectral grade or distilled prior to use. Reactions were carried out under inert gas (Ar) by using the Schlenk technique. 1,2-Dioxane was dried by distillation from a sodium/benzophenone suspension and zinc(II) iodide was sublimed in high vacuum prior to use. Gas-chromatographic analytics were executed on a Thermo Trace GC Ultra equipped with Combi PAL auto sampler and coupled with a FID and a Thermo Polaris Q electron impact (EI) – ion-trap mass spectrometer. We used a SGE forte capillary column BPX5 30 m; 0.25 mm inner diameter and 0.25 μm film. The column was operated with helium carrier gas 1.5 mL/min and split injection (injector temperature 200 °C, detector temperature 250 °C after initial 1 min at 40 °C the oven temperature was raised to 100 °C with 30 °C/min and then to 300 °C with 10 °C/min. Total ion count (TIC) was obtained using the mass range of 50–650 amu; FID temperature: 250 °C. Reaction progress was monitored by GC/FID-MS or thin layer chromatography (TLC; silica gel on aluminum sheets with fluorescent dye 254 nm, Merck KGaA). All test reactions were executed in 5 mL HPLC vials with a PTFE-coated rubber seal. NMR spectra were recorded in deuterated solvents on a Bruker AVANCE II 300 or 400 MHz instrument. The chemical shifts are reported in ppm relative to the solvent residual peak; 1H NMR (CDCl3): δ = 7.24 ppm, 13C NMR (CDCl3): δ = 77.23 ppm, 1H NMR (DMSO-d 6) δ = 2.50 ppm, 13C NMR (DMSO-d 6) δ = 39.52 ppm. Following abbreviations are used for multiplicities of resonance signals: s = singlet, d = doublet, br = broad. ESI-HRMS measurements were conducted on a Thermo Q Exactive plus apparatus.
    • 19b Methyl 2-bromo-5-hydroxybenzoate (4, 1.25 g, 5.41 mmol, 1 equiv), Cu(I)I (103 mg, 541 mmol, 0.1 equiv), Zn(II)I2 (1.9 g, 5.95 mmol, 1.1 equiv), and NaI (892 mg, 5.95 mmol, 1.1 equiv) were placed into a laboratory autoclave and flushed three times with argon. Then, 1,4-dioxane (50 mL) and N 1,N 2-dimethyl­ethane-1,2-diamine (5, 136 μL, 1.08 mmol, 0.2 equiv) were added, and the autoclave was sealed. After 24 h at 120 °C (the pressure within the autoclave rises not above 2 bar) the solvent was evaporated under reduced pressure. The white residue was taken up in water (100 mL) and extracted three times with EtOAc (100 mL). The combined organic phases were dried over sodium sulfate and concentrated to dryness under reduced pressure. The product was recrystallized from a mixture of cyclohexane and EtOAc (200 mL, 4:1 v/v). The title compound 7 was isolated in 66% yield by filtration as white solid (990 mg, 3.56 mmol). Rf = 0.31 (silica gel 60; CHCl3–MeOH = 95:5). 1H NMR (600 MHz; CDCl3): δ = 7.76 (d, 1 H, CH-3, 3 J H–H = 8.6 Hz), 7.31 (d, 1 H, CH-6, 3 J H–H = 8.6 Hz, 4 J H–H = 3.0 Hz), 6.70 (dd, 1 H, CH-4, 4 J H–H = 3.0 Hz), 5.87 (s, 1 H, OH), 3.90 (s, 3 H, COOCH3) ppm. 13C NMR (150 MHz, CDCl3): δ = 167.2 (C=O), 155.8 (C–OH), 142.1 (CH, C-3), 135.8 (C, C-1a), 120.7 (CH, C-4), 118.4 (CH, C-6), 82.1 (C-I), 52.7 (COOCH3) ppm. IR (ATR): ν (%T) = 3844 (w), 3742 (w), 3679 (w), 3319 (m), 2954 (w), 1706 (s), 1559 (s), 1463 (s), 1430 (m), 1256 (s), 1217 (s), 1094 (s), 1009 (m), 980 (m), 812 (m), 672 (m) cm–1. ESI-MS (ESI+): m/z = 301 (42) [M + Na]+, 333 (100) [M + Na + MeOH]+, 579 (15) [2 M + Na]+. HRMS (ESI+): m/z calcd for C8H7O3I [M + H]+: 278.9513; found: 278.9512.
  • 20 Casitas A, Canta M, Sola M, Costas M, Ribas X. J. Am. Chem. Soc. 2011; 133: 19386
  • 21 Proust N, Chellat MF, Stambuli JP. Synthesis 2011; 3083
    • 22a Uyanik M, Akakura M, Ishihara K. J. Am. Chem. Soc. 2009; 131: 251
    • 22b The methyl benzoate 7 (11.6 mg, 42 μM, 1 equiv) was placed into a round-bottom flask followed by the addition of MeOH (100 μL) and 1 N NaOH solution (200 μL, 210 μmol, 5 equiv). The progress of the reaction was monitored with TLC, and the reaction was stopped 15 min after complete consumption of the methyl ester by adding 1 N HCl (500 μL). After extraction with EtOAc (3 × 5 mL) the solvent was dried over Na2SO4 and evaporated under reduced pressure to give a pale yellow crystalline solid. The solid was dried in fine vacuum overnight yielding the title compound 5-hydroxy-2-iodobenzoic acid (3) (10.0 mg, 38 μmol, 91%). The 1H NMR data are identical to the reported values from ref. 22a. 1H NMR (400 MHz, DMSO-d 6): δ = 13.11 (br s, 1 H, COOH), 9.97 (s, 1 H, ArOH), 7.71 (d, 1 H, 3 J H–H = 8.6 Hz, ArCH-3), 7.13 (d, 1 H, 4 J H–H = 3.0 Hz, ArCH-6), 6.68 (dd, 1 H, 3 J H–H = 8.6 Hz, 4 J H–H = 3.0 Hz, ArCH-4) ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 167.8 (ArCOOH), 157.4 (ArCOH), 141.2 (ArCH-3), 137.5 (Ar C COOH), 120.2 (ArCH-4), 117.3 (ArCH-6), 80.0 (ArCI) ppm. HRMS (ESI): m/z calcd for C7H4IO3 [M – H] = 262.9211; found: 262.9208.