Palladium-Catalyzed Allylic Alkylations as Versatile Tool for Amino Acid and Peptide Modifications

Palladium-catalyzed allylic alkylations are especially suitable for the introduction of gamma,delta-unsaturated side chains into amino acids and even peptides. Glycine ester enolates are generally used as nucleophiles in these reactions, they react at a very low temperature (-78 degrees C) to give the products of isomerization-free allylation. In reactions of cis-configured allylic substrates, the olefin geometry can be transferred to the product. Because the syn position of the corresponding syn/anti pi-allyl complex formed in this case is more reactive, this isomerization-free protocol also allows regioselective and stereoselective allylations. Using stannylated allylic substrates gives metalated amino acid derivatives that are ideal substrates for subsequent Stille couplings or tin-iodine exchange reactions. If peptides are deprotonated with excess strong base, the corresponding ester or amide enolates formed can also be subjected to allylation; in this case the stereochemical outcome can be controlled by the peptide chain.