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Synlett 2011(11): 1608-1612  
DOI: 10.1055/s-0030-1260767
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Convertible Fluorous Linker Assisted Synthesis of Tetrasubstituted Furans

Asha Kadam, Stephanie B. Buckley, Trinh Dinh, Ryan Fitzgerald, Wei Zhang*
Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, Massachusetts 02125, USA
Fax: +1(617)2876030; e-Mail: wei2.zhang@umb.edu;
Further Information

Publication History

Received 24 February 2011
Publication Date:
01 June 2011 (online)

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Abstract

Tetrasubstituted furans are prepared by a three-step synthesis including condensation of a fluorous benzaldehyde with an acetophenone followed by Michael-type [3+2] cycloaddition with an 1,3-diketone and Pd-catalyzed coupling reaction for fluorous linker cleavage. The reactions are performed under microwave irradiation and the intermediate purifications are facilitated by fluorous solid-phase extraction (F-SPE).

Key words

fluorous linker - solid-phase extraction - tetrasubstituted furan - microwave reaction - multicomponent reaction - Suzuki coupling

    References and Notes

  • Selected reviews:
  • 1a Kirsch SF. Org. Biomol. Chem.  2006,  4:  2076 
    Google Scholar
  • 1b Hou XL. Yang Z. Wong HNC. In Progress in Heterocyclic Chemistry   Vol. 15:  Gribble GW. Gilchrist TL. Pergamon; Oxford: 2003.  p.167 
    Google Scholar
  • 1c Keay BA. Dibble PW. In Comprehensive Heterocyclic Chemistry II   Vol. 2:  Katritzky AR. Rees CW. Scriven EFV. Elsevier; Oxford: 1997.  p.395 
    Google Scholar
  • Recent examples:
  • 2a Calter MA. Zhu C. Lachicotte RJ. Org. Lett.  2002,  4:  209 
    Google Scholar
  • 2b Holtz E. Langer P. Synlett  2004,  1805 
    Google Scholar
  • 2c Calter MA. Phillips RM. Flaschenriem C. J. Am. Chem. Soc.  2005,  127:  14566 
    Google Scholar
  • 3 Sromek AW. Rubina M. Gevorgyan V. J. Am. Chem. Soc.  2005,  127:  10500 
    CrossrefPubMedGoogle Scholar
  • 4a Ma S. Zhang J. Lu L. Chem. Eur. J.  2003,  9:  2447 
    Google Scholar
  • 4b Suhre MH. Reif M. Kirsch SF. Org. Lett.  2005,  7:  3925 
    Google Scholar
  • 5a De Klein WJ. In Organic Synthesis by Oxidation with Metal Compounds   Mijs WJ. de Jonge CRH. Plenum; New York: 1984.  p.261 
    Google Scholar
  • 5b Badanyan SO. Melikyan GG. Mkrtchyan DA. Russ. Chem. Rev.  1989,  58:  286 
    Google Scholar
  • 5c Snider BB. Chem. Rev.  1996,  96:  339 
    Google Scholar
  • 5d Demir AS. Emrullahoglu M. Curr. Org. Chem.  2007,  4:  321 
    Google Scholar
  • Review:
  • 6a Pan X.-Q. Zou J.-P. Zhang W. Mol. Divers.  2009,  13:  421 
    Google Scholar
  • See also:
  • 6b Kagayama T. Nakano A. Sakaguchi Ishii SY. Org. Lett.  2006,  8:  407 
    Google Scholar
  • 6c Mu XJ. Zou JP. Qian QF. Zhang W. Org. Lett.  2006,  8:  5291 
    Google Scholar
  • 6d Pan X.-Q. Zou J.-P. Wang L. Zhang W. Chem. Commun.  2010,  46:  1721 
    Google Scholar
  • 7 Wang G.-W. Dong Y.-W. Wu P. Yuan T.-T. Shen Y.-B. J. Org. Chem.  2008,  73:  7088 
    CrossrefGoogle Scholar
  • 8 Ali F.-M. Caliskan R. Sahin E. Balci M. Tetrahedron  2009,  65:  1430 
    CrossrefGoogle Scholar
  • 9 Zhang W. In Microwave Methods in Organic Synthesis, Topics in Current Chemistry   Vol. 266:  Larhed M. Olofsson K. Springer; Berlin: 2006.  p.145 
    Google Scholar
  • 10a Zhang W. Chem. Rev.  2009,  109:  749 
  • 10b Zhang W. In Handbook of Fluorous Chemistry   Gladysz JA. Curran DP. Horvath IT. Wiley-VCH; Weinheim: 2004.  p.222 
  • 10c Zhang W. Chem. Rev.  2004,  104:  2531 
  • 11a Zhang W. Comb. Chem. High Throughput Screening  2007,  10:  219 
    Google Scholar
  • 11b Zhang W. Lu Y. Chen CH.-T. Mol. Diver.  2003,  7:  199 
    Google Scholar
  • 11c Zhang W. Nagashima T. Lu Y. Chen CH.-T. Tetrahedron Lett.  2004,  45:  4611 
    Google Scholar
  • 11d Pirrung MC. Ghorai S. Ibarra-Rivera TR. J. Org. Chem.  2009,  74:  4110 
    Google Scholar
  • 11e Zhou H. Zhang W. Yan B.
    J. Comb. Chem.  2010,  12:  206 
    Google Scholar
  • 12 Zhang W. Nagashima T. J. Fluorine Chem.  2006,  127:  588 
    CrossrefGoogle Scholar
  • 13 Zhang W. Curran DP. Tetrahedron  2006,  62:  11837 
    CrossrefPubMedGoogle Scholar
  • 15a Zhang W. Chen CH.-T. Lu Nagashima YT. Org. Lett.  2004,  6:  1473 
    Google Scholar
  • 15b

    See also ref. 11.

14

Fluorous SPE cartridges are available from Fluorous Technologies, Inc. (www.fluorous.com) and Silicycle (www.silicycle.com).

16

General Procedure for the Synthesis of 5a: To a mixture of compound 3a (46 mg, 0.06 mmol) and β-keto ester 4b
(42 µL, 45 mg, 0.4 mmol) in AcOH (0.2 mL) were added Mn(OAc)3 (128 mg, 0.48 mmol) and Cu(OAc)2 (30 mg, 0.16 mmol). The mixture in a sealed tube was heated under microwave (Biotage Initiator 8) at 165 ˚C for 25 min. The reaction mixture was purified by F-SPE eluted with MeOH-H2O (80:20, 15 mL) and then with MeOH (20 mL). The MeOH fraction was concentrated to give 5a (44 mg) in
84% yield. An analytical sample was obtained by further purification by flash chromatography (EtOAc-hexane, 7:3). ¹H NMR (300 MHz, CDCl3): δ = 2.61 (s, 3 H), 3.48 (s, 3 H), 3.76 (s, 3 H), 3.80 (s, 3 H), 6.80-6.86 (m, 3 H), 7.35-7.42 (m, 2 H), 7.80 (d, J = 8.7 Hz, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 13.9, 51.6, 55.5, 56.4, 110.5, 113.4, 114.0, 115.5, 119.6, 122.7, 126.3, 130.6, 131.7, 139.0, 146.9, 151.5, 158.7, 163.3, 164.1, 191.2. LC-MS (APCI+): m/z = 879 [M + 1]+. HRMS (ES+): m/z [M + H]+ calcd for C30H20O9F17S: 879.0550; found: 879.0557.
General Procedure for the Synthesis of 7c: A mixture of 5a (75 mg, 0.085 mmol) and p-tolylboronic acid (17 mg, 0.125 mmol), Pd(dppf)Cl2 (8.5 mg, 8 mol%) and Cs2CO3 (55 mg, 0.16 mmol) in co-solvent of acetone-H2O-HFE7200 (C4F9OEt) (4:1:4) in a sealed tube was heated under microwave (Biotage Initiator 8) at 130 ˚C for 30 min. The reaction mixture was purified by flash chromatography (EtOAc-hexanes, 7:3) to give 7c (23 mg) in 59% yield. ¹H NMR (300 MHz, CDCl3): δ = 2.30 (s, 3 H), 2.60 (s, 3 H), 3.50 (s, 3 H), 3.68 (s, 3 H), 3.77 (s, 3 H), 6.75-6.84 (m, 3 H), 7.12 (d, J = 8.1 Hz, 2 H), 7.22 (m, 2 H), 7.35 (d, J = 2.4 Hz, 1 H), 7.44 (d, J = 4.2 Hz, 1 H), 7.80 (d, J = 9.4 Hz, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 13.9, 21.3, 51.5, 55.6, 56.7, 111.3, 114.0, 115.3, 122.0, 125.9, 128.4, 128.8, 129.0, 129.4, 130.9, 131.1, 131.8, 134.9, 137.0, 149.2, 156.8, 158.1, 163.6, 163.9, 191.7. LC-MS (APCI+): m/z = 471
[M + 1]+. HRMS (ES+): m/z [M + H]+ calcd for C29H27O6: 471.1806; found: 471.1808.
General Procedure for the Synthesis of 9a: Compound 5a (60 mg, 0.068 mmol), Pd2 (dba)3 (0.32 mg, 5 mol%), JohnPhos (0.20 mg, 10 mol%) and DBU (252 µL, 0.17 mmol) were added to the flask under a nitrogen atmosphere. Then p-trifluoromethylaniline (81 µL, 0.08 mmol) in toluene (0.2 mL) was added. The mixture in a sealed tube was heated under microwave (Biotage Initiator 8) at 130 ˚C for 30 min. The reaction mixture was purified by flash chromatography (EtOAc-hexanes, 7:3) to give 9a (25 mg) in 69% yield. ¹H NMR (300 MHz, CDCl3): δ = 2.60 (s, 3 H), 3.47 (s, 3 H), 3.77 (s, 3 H), 3.78 (s, 3 H), 6.18 (s, 1 H), 6.74-6.87 (m, 5 H), 7.09-7.18 (m, 3 H), 7.28-7.34 (m, 1 H), 7.80 (d, J = 9.0 Hz, 2 H).¹³C NMR (75 MHz, CDCl3): δ = 14.0, 51.5, 55.5, 55.8, 110.9, 113.2, 114.0, 115.2, 116.3, 116.9, 117.3, 119.0, 119.4, 122.0, 126.7, 126.7, 130.9, 131.2, 131.8, 145.4, 149.1, 158.2, 163.5, 164.0, 191.7. LC-MS (APCI+): m/z = 540 [M + 1]+. HRMS (ES+): m/z [M + H]+ calcd for C29H25F3NO6: 540.1632; found: 540.1634.