Synthesis of Furo[3,4-c]furanones via DDQ Treatment of Furo[3,4-c]pyranone Derivatives

Abstract

A new method for the synthesis of 4,6-disubstituted furo[3,4-c]furanones is described. The title compounds are obtained by simple treatment of furo[3,4-c]pyranones with DDQ; furo[3,4-c]furanones are obtained in moderate yields. A possible mechanism for the conversion is discussed.

Key words

furo[3,4-c]furanones - furo[3,4-c]pyranones - 2,3-di­chloro-5,6-dicyano-1,4-benzoquinone (DDQ)

References and Notes

• 1 Corrie JET. Green GH. Ritchie E. Taylor WC. Aust. J. Chem.  1970,  23:  133 
• 2 Gonzalez AG. Estevezreyes R. Mato C. J. Nat. Prod.  1989,  52:  1139 
• 3 Cooper R. Gottlieb HE. Lavie D. Levy EC. Tetrahedron  1979,  35:  861 
• 4 Matsunaga K. Shibuya M. Ohizumi Y. J. Nat. Prod.  1994,  57:  1734 
• 5 Tatlock JH. Linton MA. Hou XJ. Kissinger CR. Pelletier LA. Showalter RE. Tempczyk A. Villafranca JE. Bioorg. Med. Chem. Lett.  1997,  7:  1007 
• 6 Fuhrer C. Messer R. Häner R. Tetrahedron Lett.  2004,  45:  4297 
• 7 Fuhrer CA. Grüter E. Ruetz S. Häner R. ChemMedChem  2007,  2:  441 
• 8 Nightingale DV. Sukornick B. J. Org. Chem.  1959,  24:  497 
• 9 Padwa A. Straub CS. J. Org. Chem.  2003,  68:  227 
• 10 For example, see: Bharate SB. Synlett  2006,  496 

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Representative Analytical Data of Furo[3,4-c]furanones; Compound 2: pale-yellow solid; mp 172-175 ˚C. ^¹H NMR (300 MHz, DMSO-d ₆): δ = 8.13-8.16 (m, 2 H), 7.60-7.62 (m, 2 H), 7.47-7.51 (m, 2 H), 7.35 (m, 1 H), 7.11-7.13 (m, 2 H), 5.59 (s, 2 H), 3.83 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 164.37 (C), 160.70 (C), 149.78 (C), 140.77 (C), 129.08 (2 × CH), 128.70 (C), 128.48 (C), 127.86 (CH), 127.17 (2 × CH), 123.79 (2 × CH), 120.62 (C), 114.70 (2 × CH), 114.15 (C), 65.85 (CH₂), 55.38 (CH₃). EI-MS:
m/z = 306. HRMS (ESI): m/z [M + H ⁺] calcd for C₁₉H₁₅O₄: 307.0970; found: 307.0965. Detailed ^¹H, ^¹³C NMR and 2D NMR (COSY, HSQC and HMQC) analysis were used for further structural assignment. The following NMR signals were observed: three sets of 12 aromatic carbons (9 of which are H-substituted), one methylene group [δ_H = 5.59 (s, 2 H) and δ_C = 65.85], methoxyl group [δ_H =3.83 (s, 3 H) and δ_C = 55.38] and carbonyl group [δ_C = 164.37], nine aromatic protons and 12 carbons on two phenyl rings at [δ_{H2 ′ ,H6 ′} = 7.60-7.62 (m, 2 H) and δ_{C2 ′ ,C6 ′} = 123.79 × 2], [δ_{H3 ′ ,H5 ′} = 7.47-7.51 (m, 2 H) and δ_{C3 ′ ,C5 ′} = 129.08 × 2], [δ_{H4 ′} = 7.35 (m, 1 H) and δ_{C4 ′} = 127.86], [δ_{H2 ′′ ,H6 ′′} = 8.13-8.16 (m, 2 H) and δ_{C2 ′′ ,C6 ′′} = 127.17 × 2], [δ_{H3 ′′ ,H5 ′′} = 7.11-7.13 (m, 2 H) and δ_{C3 ′′ ,C5 ′′} = 114.70 × 2], and [δ_{C1 ′} = 128.48 and δ_{C1 ′′} = 120.62], carbons of the furan ring at [δ_C4 = 140.77, δ_C6 = 149.78, δ_C3a = 114.15 and δ_C6a = 128.70].
Compound 6a: white solid; mp 195-197 ˚C. ^¹H NMR (300 MHz, acetone-d ₆): δ = 8.28-8.31 (m, 2 H), 7.68-7.72 (m, 2 H), 7.47-7.59 (m, 5 H), 7.38 (m, 1 H), 5.64 (s, 2 H). ^¹³C NMR (75 MHz, acetone-d ₆): δ = 150.81 (C), 135.48 (C), 130.80 (CH), 130.02 (2 × CH), 129.94 (2 × CH), 129.88 (C), 129.42 (C), 129.01 (2 × CH), 128.84 (C), 127.65 (CH), 127.45 (CH), 126.47 (2 × CH), 125.06 (CH), 66.62 (CH₂). EI-MS: m/z = 276. HRMS (ESI): m/z [M + H⁺] calcd for C₁₈H₁₃O₃: 277.0865; found: 277.0859.
Compound 6b: yellow solid; mp 177-179 ˚C. ^¹H NMR (300 MHz, acetone-d ₆): δ = 8.25-8.28 (m, 2 H), 7.63-7.66 (m, 2 H), 7.51-7.57 (m, 2 H), 7.45 (m, 1 H), 7.06-7.09 (m, 2 H), 5.59 (s, 2 H), 3.86 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 164.73 (C), 159.63 (C), 150.14 (C), 142.45 (C), 129.68 (CH), 128.94 (2 × CH), 128.51 (C), 126.15 (C), 125.74 (2 × CH), 125.52 (2 × CH), 121.96 (C), 115.84 (C), 114.69 (2 × CH), 65.59 (CH₃), 55.42 (CH₂). EI-MS: m/z = 306. HRMS (ESI): m/z [M + H⁺] calcd for C₁₉H₁₅O₄: 307.0970; found: 307.0965.
Compound 6c: white solid; mp 165-167 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 8.12-8.14 (m, 2 H), 7.42-7.52 (m, 4 H), 7.28-7.34 (m, 3 H), 5.43 (s, 2 H), 2.41 (s, 3 H). EI-MS: m/z = 290. HRMS (ESI): m/z [M⁺] calcd for C₁₉H₁₄O₃: 290.0943; found: 290.0937.
Compound 6d: white solid; mp 176-178 ˚C. ^¹H NMR (300 MHz, acetone-d ₆): δ = 8.23-8.27 (m, 2 H), 7.44-7.53 (m, 4 H), 7.35 (m, 1 H), 7.16-7.22 (m, 2 H), 5.46 (s, 2 H).
EI-MS: m/z = 294. HRMS (ESI): m/z [M + H⁺] calcd for C₁₈H₁₂FO₃: 295.0770; found: 295.0765.
Compound 6e: amorphous yellow solid. ^¹H NMR (300 MHz, acetone-d ₆): δ = 8.28-8.33 (m, 2 H), 7.61-7.64 (m, 2 H), 7.29-7.35 (m, 2 H), 7.04-7.08 (m, 2 H), 5.59 (s, 2 H), 3.86 (s, 3 H). EI-MS: m/z = 324. HRMS (ESI): m/z [M⁺] calcd for C₁₉H₁₃FO₄: 324.0798; found: 324.0792.
Compound 6f: amorphous white solid. ^¹H NMR (300 MHz, acetone-d ₆): δ = 8.33-8.38 (m, 2 H), 7.67-7.70 (m, 4 H), 7.32-7.38 (m, 2 H), 5.63 (s, 2 H). EI-MS: m/z = 372. HRMS (ESI): m/z [M + H⁺] calcd for C₁₈H₁₁BrFO₃: 372.9876; found: 372.9870.
Compound 6g: yellow solid; mp 178-181 ˚C. ^¹H NMR (300 MHz, acetone-d ₆): δ = 8.22-8.25 (m, 2 H), 7.08-7.11 (m, 2 H), 6.90 (s, 2 H), 5.63 (s, 2 H), 3.93 (s, 6 H), 3.89 (s, 3 H), 3.76 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 164.77 (C), 161.04 (C), 153.94 (2 × CH), 151.10 (C), 141.23 (C), 138.38 (C), 127.70 (2 × C), 127.35 (2 × C), 124.77 (C), 121.26 (C), 114.46 (2 × CH), 114.09 (C), 101.40 (2 × CH), 65.36 (CH₂), 61.02 (CH₃), 56.30 (2 × CH₃), 55.39 (CH₃).
EI-MS: m/z = 396. HRMS (ESI): m/z [M + H⁺] calcd for C₂₂H₂₁O₇: 397.1287; found: 397.1282.

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Reactions were carried out under an open atmosphere.