Stereoselective synthesis of alkenyl alpha,alpha'-bridged bis(glycines) using palladium promoted substitution in the bridge

Conformationally constrained cystine analogues have been synthesized which have an unsaturated four-carbon backbone-chain as a bridge between the alpha,alpha'-positions in two glycine units. Stereoselective synthesis of the cis and trans isomers of bis(glycines) with a 2'-butene bridge, and their 2'-bromo derivatives, is described. Palladium mediated coupling between the bromides and stannanes provided for carbo-substitution at the olefinic carbon in the bridge. N-Methyl-2-pyrrolidinone was an excellent solvent for this reaction when triphenylarsine was the ligand for palladium. Mild hydrolytic conditions furnished the methyl esters of the C-4-bridged bis(glycine) derivatives.