Synlett 2004(10): 1805-1807  
DOI: 10.1055/s-2004-829560
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 2-Alkenyl-3-alkoxycarbonylfurans by ‘Feist-Benary-Cyclo­condensation’ of (2,4-Dioxobutylidene)phosphoranes with Chloro­acetaldehyde and Subsequent Wittig Reactions

Edith Holtza,b, Peter Langer*a
a Institut für Chemie und Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Soldmannstrasse 16, 17487 Greifswald, Germany
b Institut für Organische Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany
e-Mail: peter.langer@uni-greifswald.de;
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Publikationsverlauf

Received 19 February 2004
Publikationsdatum:
15. Juli 2004 (online)

Abstract

Functionalized furans were prepared by ‘Feist-Benary-cyclocondensation’ of (2,4-dioxobutylidene)phosphoranes with chloroacetaldehyde and subsequent Wittig reactions.

    References

  • 1 Römpp Lexikon Naturstoffe   Steglich W. Fugmann B. Lang-Fugmann S. Thieme; Stuttgart: 1997. 
  • 2 For a review of Feist-Benary and related furan syntheses, see: Friedrichsen W. In Comprehensive Heterocyclic Chemistry   Vol. 2:  Katritzky AR. Rees CW. Scriven EFV. Elsevier; Amsterdam: 1996.  p.359-363  ; and references cited therein
  • For pharmacologically relevant 2-alkenyl-3-alkoxy-carbonyl-furans, see:
  • 3a Vuligonda V. Garst ME. Chandraratna RAS. Bioorg. Med. Chem. Lett.  1999,  9:  589 
  • 3b Rivalle C. Andre-Louisfert J. Bisangni E. Tetrahedron  1976,  32:  829 
  • For reactions of (2,4-dioxobutylidene)phosphoranes, see:
  • 4a Hatanaka M. Tanaka Y. Ueda I. Tetrahedron Lett.  1995,  3719 
  • 4b Banwell MG. Cameron JM. Tetrahedron Lett.  1996,  525 
  • 4c Hatanaka M. Ishida A. Tanaka Y. Ueda I. Tetrahedron Lett.  1996,  401 
  • 4d Ceccarelli S. Piarulli U. Gennari C. Tetrahedron Lett.  1999,  153 
  • 4e Langer P. Holtz E. Synlett  2003,  402 ; and references cited therein
  • For synthetic applications of (furylmethylidene)phos-phoranes, see:
  • 5a Cooper JA. Cornwall P. Dell CP. Knight DW. Tetrahedron Lett.  1988,  29:  2107 ; and references cited therein
  • 5b Krapivin GD. Val’ter NI. Zavodnik VE. Kaklyugina TY. Kul’nevich VG. Chem. Heterocycl. Compd.  1994,  30:  296 ; Khim. Geterotsikl. Soedin. 1994, 3: 335
  • 5c Brittain JM. Jones RA. Tetrahedron  1979,  35:  1139 
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6

Typical Procedure: To a CH2Cl2 solution (20 mL) of chloroacetaldehyde (93 mg, 1.2 mmol, 45% aq solution) was added MgSO4. The solution was filtered and the MgSO4 was washed with CH2Cl2. The filtrate (50 mL) was added to 1a (434 mg, 1.1 mmol) and the solution was refluxed for 24 h. The solvent was removed in vacuo and the residue was purified by chromatography (silica gel, eluents: acetone then MeOH, Ø = 2.0 cm) to give 3a as a colorless solid (359 mg, 72%). 1H NMR (250 MHz, CDCl3): δ = 1.10 (d, 3 J = 6 Hz, 6 H, CH3), 4.81 [sept, 3 J = 6 Hz, 1 H, OCH(CH3)2], 6.06 (d, 2 J H-P = 15 Hz, 2 H, P-CH2), 6.47 (d, 3 J = 2 Hz, 1 H, 4-H, Hetar), 7.23 (d, 3 J = 2 Hz, 1 H, Hetar), 7.35-7.55 (m, 3 H, Ph), 7.55-7.70 (m, 6 H, Ph), 7.70-7.85 (m, 6 H, Ph).
13C NMR (50.3 MHz, CDCl3): δ = 21.61 (CH3), 24.34 (d, 1 J C-P = 51 Hz, P-CH2), 68.31 [OCH(CH3)2], 110.80 (CH, d, 4 J C-P = 3 Hz, C-4, Hetar), 117.59 (C, d, 1 J C-P = 86 Hz, Ph to P), 118.68 (C, d, 3 J C-P = 8 Hz, C-3, Hetar), 130.05 (CH, d, 2 J C-P = 13 Hz, Ph, ortho to P), 133.99 (CH, d, 3 J C-P = 10 Hz, Ph, meta to P), 135.02 (CH, d, 4 J C-P = 3 Hz, Ph, para to P), 143.28 (CH, d, 4 J C-P = 3 Hz, C-5, Hetar), 148.38 (C, d,
2 J C-P = 12 Hz, C-2, Hetar), 161.75 (C, d, 4 J C-P = 3 Hz, C=O). IR (KBr): 3055 (w), 2983 (w), 2916 (w), 2749 (w), 1718 (s), 1438 (m), 1307 (m), 1197 (m), 1181 (m), 1110 (s), 743 (m), 721 (m), 693 (m), 542 (m), 511 (m) cm-1. MS (ESI, MeOH): m/z = 429 (100) [M Cl]+; the exact molecular mass m/z = 429.1612 ± 2 mD [M Cl]+ for C27H26PO3 was confirmed by HRMS (ESI, MeOH). All compounds gave satisfactory spectroscopic and analytical and/or high resolution mass data.

7

Typical Procedure: To a THF solution (5 mL) of 3a (411 mg, 0.9 mmol) was added n-BuLi (0.9 mmol, 1.0 equiv) at 0 °C. The solution was stirred for 0.5 h at 0 °C. 3,4-Di-methoxybenzaldehyde (150 mg, 0.9 mmol) was added and the mixture was stirred for 0.5 h at 0 °C. The mixture was poured into ice water (40 mL) and Et2O (100 mL) was added. The layers were separated and the aqueous layer was extracted with Et2O (50 mL). The combined organic layers were dried (MgSO4), filtered and the solvent of the filtrate was removed in vacuo. The residue was purified by chromatography (pentane-Et2O = 5:1, Rf = 0.25, Ø = 2.0 cm) to give 5e as an orange oil (204 mg, 73%, E/Z >98:2). 1H NMR (250 MHz, CDCl3): δ = 1.37 (d, 3 J = 6 Hz, 6 H, CH3), 3.90 (s, 3 H, OCH3), 3.93 (s, 3 H, OCH3), 5.20 [sept, 3 J = 6 Hz, 1 H, OCH(CH3)2], 6.73 (d, 3 J = 2 Hz, 1 H, 4-H, Hetar), 6.85 (d, 3 J = 9 Hz, 1 H, Ar), 7.10-7.20 (m, 2 H, Ar), 7.24 (d, 3 J (E) = 16 Hz, 1 H, CH=CH), 7.29 (d, 3 J = 2 Hz, 1 H, 5-H, Hetar), 7.55 (d, 3 J (E) = 16 Hz, 1 H, CH=CH).
13C NMR (75.5 MHz, CDCl3): δ = 22.04 (CH3), 55.78, 55.91 (OCH3), 67.75 [OCH(CH3)2], 108.65, 111.06, 113.66, 120.96, 131.89 (CH, Ar, CH=CH), 111.87 (CH, C-4, Hetar), 113.98 (C, C-3, Hetar), 129.49 (C, Ar), 140.92 (CH, C-5, Hetar), 149.10, 149.64 (C to O, Ar), 157.05 (C, C-2, Hetar), 163.23 (C, C=O). MS (EI, 70 eV): m/z = 316 (100) [M+], 274 (28). Anal. Calcd for C18H20O5: C, 68.34; H, 6.37. Found: C, 68.04; H, 6.01.