AN APPROACH TO THE C(17)-C(24) FRAGMENT OF BRYOSTATINS - APPLICATIONSOF STEREOSELECTIVE TRISUBSTITUTED ALKENE FORMATION BY PALLADIUM(0) CATALYZED COUPLING OF ENOL ACETATES AND VINYLIC BROMIDES

The enol acetate 26 couples stereospecifically with the vinylic bromid es 25 and 29 in the presence of tributyltin methoxide and a catalytic amount of dichlorobis(tri-o-tolylphosphine)palladium to give the beta gamma-unsaturated ketones 27 and 30 with retention of double-bond posi tion and geometry. The beta gamma-unsaturated ketone 42 which has ster eochemistry and functionality corresponding to the C(17) C(24) fragmen t of the C(20)-deoxybryostatins, is similarly prepared from the enol a cetate 26 and the vinylic bromide 41 and can be deprotected to give th e hydroxyketone 43.