HFC-134a as a fluorinated building block: short syntheses of α-fluoroenones

Author:

Bainbridge J.Marie,Corr Stuart,Kanai Masatomi,Percy Jonathan M

Publisher

Elsevier BV

Subject

Organic Chemistry,Drug Discovery,Biochemistry

Reference13 articles.

1. (a) Normant, J.-F.; Foulon, J. P.; Masure, D.; Sauvêtre, R.; Villieras, J. Synthesis 1975, 122–125. (b) Chuit, C.; Sauvêtre, R.; Masure, D.; Baudry, M.; Normant, J.-F.; Villieras, J. J. Chem. Res. (S) 1977, 104. (c) Sauvêtre, R.; Masure, D.; Chuit, C.; Normant, J.-F. Synthesis 1978, 128–130.

2. Burdon, J.; Coe, P. L.; Haslock, I. B.; Powell, R. L. Chem. Commun. 1996, 49–50.

3. Lu, L.; Pedersen, S. D.; Liu, Q.; Narske, R. M.; Burton, D. J. J. Org. Chem. 1997, 62, 1064–1071 and references cited therein.

4. Fujita, M.; Obayashi, M.; Hiyama, T. Tetrahedron 1988, 44, 4135–4145.

5. Preparation of 3a. n-Butyllithium (20.0 ml of a 1.8 M solution in hexane, 36 mmol) was added dropwise to a stirred solution of HFC-134a (600 ml, 25 mmol) in THF (30 ml) at −78°C. After 1 h, trimethylsilyl chloride (2.3 ml, 18 mmol) was added dropwise, then 1 h later, n-butyllithium (11.0 ml of a 1.8 M solution in hexane, 20 mmol) was added dropwise. The reaction was stirred at −78°C for 1 h and then warmed to −30°C, then quenched after 30 min with saturated aqueous ammonium chloride. Extractive work-up and concentration then filtration though an alumina column (Brockmann, activity 1) eluting with pentane afforded silane 3a (2.82 g, 81%) as a colourless oil. Preparation of 5a. TASF (0.43 g, 1.4 mmol) was added gradually to a stirred solution of silane 3a (1.3 g, 7.0 mmol) and benzaldehyde (0.82 ml, 7.7 mmol) in THF (14 ml) at −30°C under argon over 24 h. Dilute HCl (15 ml of a 1 M solution, 2.1 equiv.) was added and the mixture was stirred for 15 min before extractive work-up. Column chromatography (Rf 0.26, 10% diethyl ether, 90% petroleum ether) and recrystallisation from diethyl ether/hexane afforded 5a (0.74 g, 51%) as white needles, mp 52–53°C.

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