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Synlett 2003(3): 0387-0389
DOI: 10.1055/s-2003-37108
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Practical Radical Based Access to Functionalised Geminal Bisphosphonates

Fabien Gagosz, Samir Z. Zard*
Laboratoire de Synthèse Organique associé au CNRS, Ecole Polytechnique, 91128 Palaiseau, France
Fax: +33(1)69333851; e-Mail: zard@poly.polytechnique.fr.;
Further Information

Publication History

Received 18 December 2002
Publication Date:
07 February 2003 (online)

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Abstract

Xanthate derivatives of tetraalkylmethylenebisphos­phonate add efficiently to various functionalised olefins to give the corresponding adducts via a radical chain reaction initiated by a small amount of lauroyl peroxide.

Key words

bisphosphonates - xanthates - radical reactions

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10

Procedure for the Synthesis of Xanthate 1a: To a solution of tetramethylmethylenebis-phosphonate (1.16 g, 5 mmol) in anhyd THF (50 mL) at r.t. under argon was added portionwise 60% NaH in mineral oil (0.4 g, 10 mmol). When the evolution of hydrogen ceased, the reaction mixture was cooled down to -78 °C and a solution of bis-ethoxythio-carbonyldisulfane (1.27 g, 5.25 mmol) in anhyd THF (10 mL) was added. The reaction mixture was then slowly warmed to r.t. A 1 M HCl solution was added (50 mL) and the mixture was extracted with diethyl ether (2 × 50 mL). The combined organic extracts were washed with sat. aq NaCl, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The residue was purified by flash column chromatography (silica gel, dichloro-methane/methanol, 97:3) to give 1a (1.28 g, 73%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ = 1.45 (t, J = 7.0 Hz, 3 H), 3.84-3.87 (m, 12 H), 4.70 (q, J = 7.0 Hz, 2 H), 4.91 (t, J = 21.7 Hz, 1 H). 13C NMR (50 MHz, CDCl3): δ = 13.8, 41.5 (t, J CP = 137 Hz), 54.4 (d, J CP = 9 Hz), 72.3, 211.9. IR (CCl4): 2955, 1459, 1264, 1239, 1184, 1112, 1042 cm-1. MS (CI + NH3): m/z = 353 (MH+), 370 (MNH4 +).

11

Typical Procedure: 352 mg (1 mmol) of xanthate 1a and 0.33 mL (2 mmol) of allyl acetate dissolved in 1,2-dichloroethane (1 mL) were refluxed a few minutes under argon before the addition of (20 mg, 0.05 mmol) of commercially available lauroyl peroxide. The reflux was maintained for another 2 h. The solvent was then removed under reduced pressure and the residue purified by flash column chromatography (silica gel, dichloromethane/methanol, 97:3) to give 2b (370 mg, 82%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ = 1.41 (t, J = 7.0 Hz, 3 H), 2.05 (s, 3 H), 2.02-2.22 (m, 1 H), 2.28-2.41 (m, 1 H), 2.66 (tdd, J = 25.0, 8.8, 3.5 Hz, 1 H), 3.78-3.82 (m, 12 H), 4.19 (dd, J = 11.1, 5.3 Hz, 1 H), 4.24-4.30 (m, 1 H), 4.34 (dd, J = 11.1, 4.1 Hz, 1 H), 4.62 (q, J = 7.0 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 13.8, 20.8, 26.3 (t, J CP = 4 Hz), 33.4 (t, J CP = 134 Hz), 48.5, 53.5 (d, J CP = 9 Hz), 65.6, 70.5, 170.6, 212.0. IR (CCl4): 2954, 1748, 1257, 1227, 1036 cm-1. MS (CI + NH3): m/z = 453 (MH+). Anal. Calcd for C13H26O9P2S2: C, 34.51; H, 5.79. Found: C, 34.61; H, 5.88.