A New Synthesis of 8-Oxabicyclo[3.2.1]octan-2-one and Its Use for the Preparation of Cycloheptane Annulated Furans

Abstract

Two novel syntheses of 8-oxabicyclo[3.2.1]octan-2-one are described, making this key intermediate readily available in preparative amounts. On chain elongation with various oxophosphonates this compound is converted to α,β-unsaturated ketones, which, on treatment with BF₃˙OEt₂, cyclize to furanocycloheptanols with a substitution pattern not reported previously.

Key words

bicyclic ketones - Wittig-Horner reactions - hetero­cycles - furan synthesis - annulated furan derivatives

References and Notes

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• 4 Gonis G. Amstutz ED. J. Org. Chem.  1962,  27:  2946 
• 5 Finan PA. J. Chem. Soc.  1963,  3917 
• 6a More JD. Finney NS. Org. Lett.  2002,  4:  3001 
• 6b For the preparation of IBX, see: Frigerio M. Santagostino M. Sputore S. J. Org. Chem.  1999,  64:  4537 
• 7 Yamada S. Morizono D. Yamamoto K. Tetrahedron Lett.  1992,  33:  4329 
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9

Representative Procedure
To a suspension of NaH (67 mg, 60% suspension in oil, 1.67 mmol, 1.05 equiv) in dry THF (10 mL), cooled to 0 ˚C, was added a solution of diethyl (2-oxopropyl)phosphonate (339 mg, 1.75 mmol, 1.1 equiv) in dry THF (10 mL) dropwise under nitrogen. After complete addition the reaction mixture was allowed to stir for 1 h at r.t. To this solution the ketone 9 (200 mg, 1.59 mmol, 1 equiv) was added, and the mixture was allowed to stir for 24 h at r.t. The reaction was quenched by the addition of H₂O (50 mL) and worked up with Et₂O (4 × 50 mL). The combined extracts were dried over anhyd Na₂SO₄ and concentrated. The residue was purified by column chromatography (Et₂O-pentane, 1:1) to afford the HWE adduct 17a (242 mg, 92%). To the HWE adduct (100 mg, 0.6 mmol, 1 equiv) in dry CH₂Cl₂ (15 mL), was added BF₃˙OEt₂ (128 mg, 0.9 mmol, 1.5 equiv), and the solution was allowed to reflux for 6 h. The reaction was quenched by the addition of sat. NaHCO₃ solution and worked up by CH₂Cl₂ extraction. The combined extracts were dried over anhyd Na₂SO₄, filtered, and concentrated. The residue was purified by column chromatography (Et₂O-pentane, 1:1) to afford the furan 18a (82 mg, 82%) as a white amorphous solid.
Compound 18a: white amorphous solid; mp 55-57 ˚C. IR (diamond ATR): ν_max = 3333, 2941, 2920, 2981, 2581, 1578, 1493, 1442, 1251, 1022, 957, 904, 802 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 1.53-1.76 (m, 2 H), 1.86 (br s, 1 H), 1.95-2.10 (m, 2 H), 2.19 (s, 3 H), 2.25-2.40 (m, 2 H), 2.47-2.65 (m, 2 H), 2.77-2.90 (m, 1 H), 3.87 (tt, 1 H, J ₁ = 2.8 Hz, J ₂ = 9.1 Hz), 5.73 (s, 1 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 13.2, 21.0, 23.1, 34.9, 37.0, 73.4, 108.7, 120.4, 147.9, 150.0. HRMS (EI): m/z calcd for C₁₀H₁₄O₂: 166.09938; found: 166.09902.