An approach to the C(17)–C(24) fragment of bryostatins: applications of stereoselective trisubstituted alkene formation by palladium(0) catalysed coupling of enol acetates and vinylic bromides

Abstract

The enol acetate 26 couples stereospecifically with the vinylic bromides 25 and 29 in the presence of tributyltin methoxide and a catalytic amount of dichlorobis(tri-o-tolylphosphine)palladium to give the βγ-unsaturated ketones 27 and 30 with retention of double-bond position and geometry. The βγ-unsaturated ketone 42 which has stereochemistry and functionality corresponding to the C(17)–C(24) fragment of the C(20)-deoxybryostatins, is similarly prepared from the enol acetate 26 and the vinylic bromide 41 and can be deprotected to give the hydroxyketone 43.