Synlett 2004(5): 0856-0860  
DOI: 10.1055/s-2004-817781
LETTER
© Georg Thieme Verlag Stuttgart · New York

Polystyrene-bound Cinchona Alkaloids: Application to Enantioselective Electrophilic Fluorination of Silyl Enol Ethers

Baptiste Thierry, Christophe Audouard, Jean-Christophe Plaquevent, Dominique Cahard*
UMR 6014 CNRS de l’IRCOF (Institut de Recherche en Chimie Organique Fine), Université de Rouen, 1 Rue Tesnière, 76821 Mont Saint Aignan Cedex, France
e-Mail: dominique.cahard@univ-rouen.fr;
Further Information

Publication History

Received 23 December 2003
Publication Date:
17 February 2004 (online)

Abstract

A panoply of new polystyrene-bound cinchona alkaloids (PS-CA) has been prepared, and exploited for the design of un­precedented enantioselective electrophilic fluorinating agents. Compared to nonsupported [N-F]+ reagents, the polystyrene-bound N-fluoro ammonium salts of cinchona alkaloids show comparable efficiency and ready purification of the fluorinated reaction ­products. One PS-CA was recycled 3 times without loss of stereo­chemical performance.

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Experimental Procedure for the Preparation of Poly [ O 9 -(4-Vinylbenzoyl) Dihydroquinine] (PS-CA Type I Soluble): A solution of 4-vinylbenzoic acid (500 mg, 3.38 mmol, 1 equiv) in thionyl chloride (4.92 mL, 67.6 mmol, 20 equiv) was refluxed for 1 h. After cooling the mixture to r.t., the excess of thionyl chloride was removed by concentration under reduced pressure to afford 4-vinylbenzoyl chloride (562.5 mg, 3.38 mmol, brown solid). To this solid was added, under nitrogen at r.t., 20 mL of freshly distilled CH2Cl2, the dihydroquinine (3.38 mmol, 1.10 g, 1 equiv) and Et3N (470 µL, 3.38 mmol, 1 equiv). The mixture was then stirred for 15 h at r.t. Then, the reaction was quenched with H2O, and the organic layer was washed with 1 M Na2CO3 solution, brine, dried and concentrated under reduced pressure. The solid was then purified by flash chromatography (acetone-EtOAc, 4:1) to afford a white solid. O 9 -(4-Vinylbenzoyl) Dihydroquinine: Yield = 59%. 1H NMR: δ = 8.59 (d, 1 H, J = 4.5 Hz), 7.90 (m, 3 H), 7.40 (s, 1 H), 7.23 (m, 2 H), 7.20 (d, 2 H, J = 2 Hz), 6.65 (d, 1 H, J = 7 Hz), 6.53 (m, 1 H), 5.67 (d, 1 H, J = 18 Hz), 5.18 (d, 1 H, J = 11 Hz), 3.81 (s, 3 H), 3.27 (m, 1 H), 2.77 (m, 1 H), 2.62 (m, 3 H), 1.85 (m, 1 H), 1.77 (s, 1 H), 1.48-1.18 (m, 5 H), 1.07 (m, 1 H), 0.73 (t, 3 H, J = 7 Hz). 13C NMR: δ = 165.7, 158.3, 147.8, 145.1, 144.4, 142.8, 136.1, 132.1, 130.3, 129.1, 127.4, 126.6, 122.3, 119.0, 117.3, 101.8, 74.5, 59.8, 55.9, 51.1, 50.3, 37.7, 27.5, 26.5, 25.8, 23.8, 12.3. A solution of O 9-(4-vinylbenzoyl dihydroquinine (2.19 mmol) and 2,2′-azobisisobutyronitrile (7.0 mg, 0.04 mmol, 0.02 equiv) in dry benzene (20 mL) was refluxed under nitrogen atmosphere. After 48 h, the solution was cooled to r.t., concentrated to about 5 mL and poured onto Et2O. The precipitate was filtered, washed with EtOH and dried to afford the Poly [ O 9 -(4-Vinylbenzoyl) dihydroquinine]: Yield = 60%. 1H NMR: δ = 8.57 (m, 1 H), 7.77 (m, 3 H), 7.31 (m, 1 H), 7.13 (m, 2 H), 6.59 (m, 2 H), 3.76 (s, 3 H), 3.17-2.88 (m, 4 H), 2.48 (m, 1 H), 2.16 (m, 1 H), 1.52-1.01 (m, 11 H), 0.58 (m, 3 H). 13C NMR: δ = 167.0, 158.3, 147.8, 146.9, 143.2, 132.2, 128.3, 128.5, 128.2, 127.1, 122.6, 122.5, 118.7, 101.7, 74.9, 59.5, 59.4, 58.6, 58.2, 43.2, 37.6, 29.1, 28.1, 28.0, 25.7, 22.7, 12.4. [α]D 23 +197.2 (c 1.21, CHCl3). Anal. Calcd for C29H32N2O3: C, 76.03; H, 7.06; N, 6.14; O, 10.51. Found: C, 76.33; H, 7.33; N, 5.87; O, 10.47.

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Typical Experimental Procedure: To the poly [O 9-(4-VB)-DHQN] (0.25 mmol, 114.15 mg) in MeCN (1 mL) was added under nitrogen atmosphere N-fluorobenzenesulfonimide (74.4 mg, 0.224 mmol, 1 equiv), and the mixture was stirred for 1 h at r.t. Then, the solution containing the N-fluoro-bound reagent was added to a solution of trimethylsilyl enol ether 1b (0.25 mmol, 73.7 mg, 1 equiv) in THF (1 mL) at -40 °C within 2 h. The solution was stirred for 16 h, then H2O was added (9 µM, 2 equiv). The solution was concentrated under reduced pressure to a saturated solution and Et2O was added (10 mL) to cause the heterogenization. The polymer was recovered by centrifugation and extraction of the supernatant liquid. A second similar purification procedure was conducted after dissolution of the polymer in the minimun amount of CH2Cl2. The filtrates were then concentrated under reduced pressure and purified by flash chromatography (cyclohexane-Et2O, 9:1), leading to the fluorinated ketone 2b (see ref. 2d for spectroscopic data). The enantiomeric excess was then determined by HPLC using Chiracel OB column.