Stereoselective radical bromination of α-chloro hydrocinnamic acid derivatives

Reaction of (S)-2-chloro-3-phenylpropanoic acid derivatives with NBS gave the corresponding 3-bromo-2-chloro derivatives with a preference for the formation of the (2R,3S) isomers over the (2R,3R) isomers. The stereoselectivity was affected by the nature of the carboxylic acid derivative. Reaction of ester derivatives was highly stereoselective while the reaction of amide derivatives showed varied stereoselectivity which depended on the nature of the amide. Theoretical studies at UHF/3-21G* level showed that the intermediate benzylic radical of the methyl ester, the methyl amide and the diisopropyl amide derivatives had different energy profiles with respect to rotation of the C2–C3 bond. The different stereoselectivity observed from reaction of the various acid derivatives could be attributed, at least in part, to different distribution of conformers of the radical intermediate.