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

Abstract

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

Key words

chemoselectivity - cyclizations - furans - Wittig reaction

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
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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, R_f = 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.