Palladium-catalyzed double cross-coupling of E-vinylic dibromides with phZnCl and the synthesis of tamoxifen

Abstract

(E)-1,2-vinylic dibromides 11a-f were stereoselectively prepared via bromination of acetylenic compounds with pyridinium tribromide in MeOH/CCl 4 at low temperature and double cross-coupled with PhZnCl under Pd(0) catalysis (Negishi protocol) to afford tri- and tetrasubstituted olefins 14a-e. Tamoxifen, a selective estrogen receptor modulator clinically prescribed in breast cancer therapy, was prepared in 7 steps and 30% overall yield from 4-iodophenol (3) as a 2.3:1 mixture of (Z)- and (E)-isomers.