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Synlett 2009(11): 1733-1736  
DOI: 10.1055/s-0029-1217366
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Phosphine-Catalysed Cyclisation of β-Hydroxy-α,α-Difluoroynones

Marie Schuler, Angèle Monney, Véronique Gouverneur*
Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK
Fax: +44(1865)275644; e-Mail: veronique.gouverneur@chem.ox.ac.uk;
Further Information

Publication History

Received 9 January 2009
Publication Date:
12 June 2009 (online)

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Abstract

2-Benzylidene-4,4-difluorodihydrofuran-3(2H)-ones were synthesised in 58-86% yield via phosphine-promoted cyclisation of β-hydroxy-α,α-difluoroynones. The benzylidene group was found to be a suitable masked carbonyl group, thereby allowing for the validation of a novel route to 3,3-difluoro-2-hydroxy-γ-lactols.

Key words

phosphine - fluorine - furanone - catalysis

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For additional details on the synthesis of β-hydroxy-α,α-difluoroynones, see the Electronic Supporting Information of ref. 7.

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General Procedure for Cyclisation of 1c
To a solution of 1c (200 mg, 0.64 mmol, 1 equiv) in anhydrous toluene (64 mL) was added under argon AcOH (15 µL, 0.255 mmol, 40 mol%) followed by dppp (26.3 mg, 0.064 mmol, 10 mol%). The reaction mixture was stirred at 60 ˚C for 4 h. The crude mixture was concentrated in vacuo at r.t., and the resulting solution was directly purified by column chromatography on silica gel (hexane-Et2O, 80:20) to give the product as a yellow oil (120 mg, 0.38 mmol) in a 60% yield.



( Z )-2-Benzylidene-4,4-difluoro-5-(2-phenylethyl)-dihydrofuran-3 (2 H )-one (2c)
R f = 0.68 (hexane-EtOAc, 80:20). ¹H NMR (400 MHz, CDCl3): δ = 2.25 (q, J = 7.3 Hz, 2 H, CH 2CH), 2.91-3.04 (m, 2 H, CH2Ph), 4.44-4.55 (m, 1 H, CF2CH), 6.65 (s, 1 H, C=CHPh), 7.25-7.46 (m, 8 H, 8 × ArH), 7.79 (br d, J = 6.8 Hz, 2 H, 2 × ArH). ¹³C NMR (100 MHz, CDCl3): δ = 29.5 (d, J = 6.4 Hz, CH2), 30.8 (CH2), 79.7 (dd, J = 27.2, 24.0 Hz, CH), 112.7 (CH), 113.3 (dd, J = 268.8, 256.4 Hz, CF2), 126.6 (CH), 128.6 (CH), 128.8 (CH), 129.0 (CH), 130.0 (CH), 131.3 (CH), 132.5 (C), 140.0 (C), 144.1 (dd, J = 4.8, 3.2 Hz, C), 186.5 (t, J = 25.2 Hz, C). ¹9F NMR (377 MHz, CDCl3): δ = -125.17 (dd, J = 282.3, 14.9 Hz, 1 F), -120.62 (dd, J = 281.7, 12.1 Hz, 1 F). IR (CH2Cl2): ν = 3055, 1751, 1266, 1135, 738 cm-¹. HRMS (CI+): m/z calcd for C19H17F2O2 [M + H]+: 315.1197; found: 315.1209.

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Procedure for the Synthesis of 6c
To a stirred solution of 5c (47.6 mg, 0.11 mmol, 1 equiv) in MeCN-CCl4-H2O (1.5:1:1, 1 mL) were added NaIO4 (141 mg, 0.66 mmol, 6 equiv) and RuCl3˙H2O (0.9 mg, 4.4 µmol, 4 mol%). After 30 min, the reaction mixture was quenched by addition of H2O, and it was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. Purification by column chromatography on silica gel (hexane-Et2O, 95:5 to 90:10) gave the product as a white solid (26.5 mg, 74 µmol) in a 68% yield. R f = 0.23 (hexane-Et2O, 95:5). ¹H NMR (400 MHz, CDCl3): δ = 0.14 and 0.17 (2 × s, 6 H), 0.92 (s, 9 H), 2.05-2.15 (m, 2 H), 2.70-2.91 (m, 2 H), 4.25-4.36 (m, 1 H), 4.48 (dd, J = 14.8, 9.4 Hz, 1 H), 7.16-7.22 (m, 3 H), 7.25-7.32 (m, 2 H). ¹³C NMR (126 MHz, CDCl3): δ = -4.8 (CH3), -5.1 (CH3), 18.5 (C), 25.5 (CH3), 28.8 (d, J = 5.2 Hz, CH2), 30.7 (CH2), 71.2 (dd, J = 19.5, 19.6 Hz, CH), 77.8 (dd, J = 25.3, 24.6 Hz, CH), 120.8 (dd, J = 254.0-254.1 Hz, CF2), 126.7 (CH), 128.7 (CH), 128.9 (CH), 139.9 (C), 169.3 (d, J = 17.1 Hz, C=O). ¹9F{¹H} NMR (377 MHz, CDCl3): δ = -131.30 (d, J = 232.0 Hz, 1 F), -116.62 (d, J = 232.0 Hz, 1 F). IR (CH2Cl2): ν = 2950, 2900, 2833, 1810, 1263, 1153, 910, 735 cm-¹. MS (CI+): m/z = 374.25 [M + NH4]+.