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Synlett 2008(3): 413-417  
DOI: 10.1055/s-2008-1032045
LETTER
© Georg Thieme Verlag Stuttgart · New York

Horner-Wadsworth-Emmons Modification for Ramirez gem-Dibromoolefination of Aldehydes and Ketones Using P(Oi-Pr)3

Yuan-Qing Fang, Olga Lifchits, Mark Lautens*
Davenport Chemistry Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada
Fax: +1(416)9468185; e-Mail: mlautens@chem.utoronto.ca;
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Publication History

Received 28 September 2007
Publication Date:
16 January 2008 (online)

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Abstract

A simple procedure for the use of triisopropylphosphite in the Ramirez olefination is described. This reagent is equally or more reactive than PPh3 toward aldehydes and ketones in the gem-dibromoolefination of aldehydes and ketones. Under the reaction conditions, an α-bromoketone gave a novel tribromomethyl-substituted oxirane product in good yield. The substrate-dependent nature of this reaction suggests that this Horner-Wadsworth-Emmons equivalent of the Ramirez gem-dibromoolefination reaction proceeds through an ionic mechanism.

Key words

olefination - phosphite - Horner-Wadsworth-Emmons reaction - aldehydes - ketones

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General Procedure for Ramirez OlefinationTo a solution of 1a (0.151 g, 1 mmol) and CBr4 (0.49 g, 1.5 mmol) in CH2Cl2 (4 mL) was added dropwise a solution of the corresponding phosphine or phosphite (3.0 mmol) in CH2Cl2 (1 mL) at 0 °C. After 30 min, the reaction was warmed to r.t., quenched with NaHCO3, extracted with Et2O, and dried over MgSO4. The product was isolated using column chromatography, and yields are shown in Table [2] .Preparation of 2a Using CBr 4 /P(O i -Pr) 3 without Chromatographic PurificationTo a solution of 1a (2.0 g, 13.2 mmol) and CBr4 (6.6 g, 19.9 mmol) in CH2Cl2 (50 mL) was added dropwise a solution of P(Oi-Pr)3 (7.2 mL, 29 mmol) in CH2Cl2 (10 mL) at 0 °C. After 30 min, the reaction was warmed to r.t., quenched with NaHCO3, and extracted with Et2O. After removal of solvent, the mixture was taken into concd HCl (12 M, 15 mL) and AcOH (15 mL) and heated to reflux overnight. The mixture was cooled to r.t., diluted with H2O (50 mL), neutralized with Na2CO3, and extracted with Et2O. After drying over MgSO4, solvent was removed under vacuum to give an off-white solid (3.51 g, 87%). The 1H NMR spectrum of the product was identical to the authentic sample.Compound 2f: The general procedure was followed using 1f (0.135 g, 0.5 mmol), CBr4 (0.250 g, 0.75 mmol), and P(Oi-Pr)3 (0.37 mL, 1.5 mol). The product was obtained as a slightly yellow solid (0.207 g, 98%). R f = 0.41 (10% EtOAc in hexane); mp 63-65 °C. IR (neat): 3079, 2921, 1624, 1528, 1347, 1254, 1099 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.28-8.36 (2 H, m), 7.47-7.49 (2 H, m), 7.28-7.38 (4 H, m). 13C NMR (100 MHz, CDCl3): δ = 162.4 (J C-F = 262 Hz), 144.4, 131.8, 129.7, 128.7, 126.8 (J C-F = 4.6 Hz), 126.3 (J C-F = 10.7 Hz), 123.5, 122.1, 117.6 (J C-F = 24.5 Hz), 104.1, 98.9, 87.2. HRMS (EI): m/z calcd for C16H8Br2FNO2 [M]+: 422.8906; found: 422.8907.

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Product 4: The general procedure for Ramirez olefination was followed using α-bromoacetophenone (1.08 g, 5.4 mmol), CBr4 (3.54 g, 10.8 mmol), and P(Oi-Pr)3 (5.3 mL, 21.6 mol). The product was obtained as a white crystalline solid (1.5 g, 80%). The single crystal suitable for X-ray determination was obtained by slow diffusion of hexanes in a solution of 4 in CH2Cl2. R f = 0.70 (10% EtOAc in hexane); mp 98-100 °C. IR (neat): 3017, 1582, 1447 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.80-7.82 (2 H, m), 7.36-7.42 (3 H, m), 3.84 (1 H, d, J = 5.0 Hz), 3.12 (1 H, d, J = 5.0 Hz). 13C NMR (100 MHz, CDCl3): δ = 133.3, 131.2, 129.4, 127.7, 67.8, 55.4, 45.8. HRMS (EI): m/z calcd for C9H7Br3O [M]+: 367.8047; found: 367.8041.

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The general procedure for Ramirez olefination was followed using phenylpropynal (0.130 g, 1 mmol), CBr4 (0.498 g, 1.5 mmol), and P(Oi-Pr)3 (0.74 mL, 3 mol) in CH2Cl2 at -20 °C. The crude material was separated by chromatography to give 6 (0.136 g, 47%) and 7 (0.232 g, 50%).Compound 6: 1H NMR (400 MHz, CDCl3): δ = 7.33-7.52 (5 H, m), 6.77 (1 H, s).Compound 7: R f = 0.22 (25% EtOAc in hexane). IR (neat): 2980, 2934, 2211, 1572, 1488, 1375, 1280, 1158 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.50-7.57 (2 H, m), 7.33-7.42 (3 H, m), 4.84 (2 H, septet, J = 6.2 Hz), 1.39 (12 H, t, J = 6.0 Hz). 13C NMR (100 MHz, CDCl3): δ = 131.8, 129.8, 128.6, 121.4, 99.7, 91.4 (d, J C-P = 11.8 Hz), 81.3 (d, J C-P = 2.4 Hz), 79.1 (d, J C-P = 4.3 Hz), 74.2 (d, J C-P = 6.3 Hz), 23.8 (d, J C-P = 4.6 Hz), 23.7 (d, J C-P = 5.4 Hz). 31P NMR (300 MHz, CDCl3): δ = -9.44. ESI-HRMS: m/z calcd for C16H20O4PBr2 [M + H]+: 464.9460; found: 464.9458.