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Synlett 2005(17): 2627-2630  
DOI: 10.1055/s-2005-917113
LETTER
© Georg Thieme Verlag Stuttgart · New York

Addition of Ethyl Bromodifluoroacetate to Lactones: Reactivity and ­Stereoselectivity

Ana B. Cuenca, François D’Hooge, Vanessa Gouge, Géraldine Castelot-Deliencourt, Hassan Oulyadi, Eric Leclerc, Philippe Jubault, Xavier Pannecoucke*, Jean-Charles Quirion*
IRCOF, LHO, UMR CNRS 6014, Université et INSA de Rouen, Rue Lucien Tesnière, 76131 Mont-Saint-Aignan, France
e-Mail: xavier.pannecoucke@insa-rouen.fr; e-Mail: jean-charles.quirion@insa-rouen.fr;
Further Information

Publication History

Received 23 August 2005
Publication Date:
05 October 2005 (online)

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Abstract

Reformatsky-type additions, under various metal­mediated activation, of ethyl bromodifluoroacetate toward a series of unactivated lactones and various sugar lactones proceeded with medium to good yields and in a completely diastereoselective ­manner.

Key words

addition reactions - fluorine - lactones - carbohydrates - stereoselectivity

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Method A. To a suspension of zinc [19] (7 equiv, 15.7 mmol) in anhyd THF (31 mL) warmed to reflux temperature were added ethyl bromodifluoroacetate (3 equiv, 6.7 mmol) and the desired lactone (1 equiv, 2.24 mmol) in anhyd THF (31 mL). The reaction was stirred at the same temperature under inert atmosphere during a variable period between 2.30-4 h depending of the substrate. The resulting mixture was then diluted with 1 N aq HCl and stirred for 10 min before extraction with CH2Cl2. The extracts were dried over anhyd MgSO4. After removal of the solvent under reduced pressure, the crude mixture thus obtained was subjected to flash silica gel chromatography.
Method B.
To a suspension of zinc (7 equiv, 7 mmol) in anhyd THF (12 mL) was added Cp2TiCl2 (0.05 equiv, 0.05 mmol) at r.t. The initial reddish color was turned to easily identifiable green color after 2-3 min, the corresponding lactone (1 equiv, 1 mmol) was then added in anhyd THF (12 mL). Finally ethyl bromodifluoroacetate (5 equiv, 5 mmol) in anhyd THF (6 mL) was added. The reaction was stirred at the same temperature under inert atmosphere for 12 h. The resulting mixture was then diluted with 1 N aq HCl and stirred for 10 min before extraction with CH2Cl2. The extracts were dried over anhyd MgSO4. After removal of the solvent under reduced pressure, the crude material thus obtained was subjected to flash silica gel chromatography.
Method C.
To a mixture of (3.5 equiv, 1.33 mmol) of Zn and CeCl3 (0.06 equiv, 0.023 mmol) in anhyd THF (3 mL) was added a solution of the required lactone (1 equiv, 0.38 mmol) in anhyd THF (6 mL) at r.t. Ethyl bromodifluoroacetate (3 equiv, 1.8 mmol) was added. The reaction mixture was stirred at the same temperature under inert atmosphere for 2-3 h. The resulting mixture was then diluted with 1 N aq HCl and stirred for 10 min before extraction with CH2Cl2. The extracts were dried over anhyd MgSO4. After removal of the solvent under reduced pressure, the crude material thus obtained was subjected to flash silica gel chromatography.
Method D.
To a solution of the required lactone (0.22 mmol, 1 equiv) in anhyd and degassed THF (20 mL) was added, at r.t. and under argon, ethyl bromodifluoroacetate (0.66 mmol, 3 equiv). At this moment, a 0.037 M solution of SmI2 (50 mL, 8.40 equiv) was added, at r.t., until the blue color persisted. The reaction was stirred at the same temperature until the blue color disappeared and the mixture turned yellow. The resulting mixture was poured into a solution of NaHCO3 (30 mL) and stirred for 10 min before extraction with CH2Cl2. The extracts were dried over anhyd MgSO4. After removal of the solvent under reduced pressure, the crude material thus obtained was subjected to flash silica gel chromatography.

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Ethyl 2-{(2 R ,3 R ,4 S ,5 R ,6 R )-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]-tetrahydro-2-hydroxy-2 H -pyran-2-yl}-2,2-difluoroacetate ( 10). Procedure A: column chromatography (cyclohexane-EtOAc = 25:1) of the crude product gave a colorless syrup (73%); [α]D 20 +49.8 (c 0.616, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.23-7.17 (m, 18 H), 7.12-7.09 (m, 2 H), 4.80 (s, 1 H), 4.73 (m, 4 H), 4.55-4.37 (m, 3 H), 4.15 (q, 2 H, J = 7.17 Hz), 4.10 (m, 1 H), 3.95-3.90 (m, 3 H), 3.68-3.51 (m, 3 H), 1.16 (t, 3 H, J = 7.17 Hz). 13C NMR (75 MHz, CDCl3): δ = 162.82 (t, 2 J CF = 30.8 Hz), 138.26, 138.16, 137.90, 137.45, 128.29, 127.82, 127.60, 127.52, 112.30 (dd, J CF = 263.6 Hz, J CF = 259.6 Hz), 96.08 (dd, J CF = 28.17 Hz, J CF = 26.4 Hz), 83.28, 78.12, 77.33, 75.88, 75.17, 74.97, 73.31, 72.54, 68.16, 63.21, 13.78. 19F NMR (282 MHz, CDCl3): δ = -119.94 (d, 1 F, J FF = 256.5 Hz), -117.63 (d, 1 F, J FF = 256.5 Hz). MS (EI): 685.3 [M + Na]. Anal. Calcd for C38H40F2O8: C, 68.87; H, 6.08. Found: C, 68.56; H, 5.79.