Stereoselective radical bromination of α-chloro hydrocinnamic acid derivatives

Author:

See Wong Leh,Chan Bun,Wui Tan Eng

Publisher

Elsevier BV

Subject

Organic Chemistry,Drug Discovery,Biochemistry

Reference9 articles.

1. Shaw, J. P.; Tan, E. W. J. Org. Chem. 1996, 61, 5635.

2. For an overview, see: Skell, P. S.; Shea, K. J. In Free Radicals; Kochi, J. K., Ed. Bridged free radicals. John Wiley & Sons: New York, 1973; Vol. II, pp. 809–852.

3. For example, see: (a) Fisher, E.; Schoeller, W. Liebigs Ann. Chem. 1907, 357, 1. (b) Renard, M. Bull. Soc. Chim. Biol. 1946, 28, 497. (c) Karrer, P.; Reschofsky, H.; Kasse, W. Helv. Chim. Acta 1947, 30, 271.

4. Typical procedure for preparation of α-chloro acid derivatives 1. A mixture of (S)-2-chloro-3-phenylpropanoic acid (4.0 g, 21.7 mmol) and PCl5 (9.0 g, 43.4 mmol) in benzene (100 ml) was heated under reflux under an anhydrous atmosphere for 2 h. The resulting solution was cooled and washed with ice-water (1×50 ml). After drying (Na2SO4), aniline (2.0 g, 21.7 mmol) and triethylamine (4.4 g, 43.4 mmol) were added to the solution and the mixture was left stirring under an anhydrous atmosphere for 2 days. The solution was washed with 1 M HCl, satd NaHCO3 and water and was then dried over Na2SO4. The solvent was removed under reduced pressure and the crude product recrystallised from hexane/ethyl acetate to give pure 1e in 24% yield. All new compounds were fully characterised.

5. Typical procedure for bromination. A mixture of phenyl (S)-2-chloro-3-phenylpropanamide 1e (20 mg, 77 mmol) and NBS (13 mg, 77 mmol) in CCl4 (5 ml) was heated at reflux under nitrogen. The reaction was initiated by irradiation with a 160 W mercury lamp. After 2 h the mixture was cooled and the solvent was removed under reduced pressure. The composition of the crude product was determined by NMR spectroscopy. All new compounds were fully characterised.

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