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.

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

5c Brittain JM. Jones RA. Tetrahedron  1979,  35:  1139 

5d Schweizer EE. Creasy WS. Light KK. Schaffer ET. J. Org. Chem.  1969,  34:  212 

5e Märkl G. Stiegler J. Kreitmeier P. Burgemeister T. Kastner F. Dove S. Helv. Chim. Acta  1997,  80:  14 

5f Tsuboi S. Mimura S. Ono S. Watanabe K. Takeda A. Bull. Chem. Soc. Jpn.  1987,  60:  1807 

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.