STEREOSELECTIVE SYNTHESIS OF ALKENYL ALPHA,ALPHA'-BRIDGED BIS(GLYCINES) USING PALLADIUM PROMOTED SUBSTITUTION IN THE BRIDGE

Conformationally constrained cystine analogues have been synthesized w hich have an unsaturated four-carbon backbone-chain as a bridge betwee n the alpha,alpha'-positions in two glycine units. Stereoselective syn thesis of the cis and trans isomers of bis(glycines) with a 2'-butene bridge, and their 2'-bromo derivatives, is described. Palladium mediat ed coupling between the bromides and stannanes provided for carbo-subs titution at the olefinic carbon in the bridge. N-Methyl-2-pyrrolidinon e was an excellent solvent for this reaction when triphenylarsine was the ligand for palladium. Mild hydrolytic conditions furnished the met hyl esters of the C-4-bridged bis(glycine) derivatives.