Palladium-catalyzed allylic alkylations are especially suitable for the introduction
of γ,δ-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 °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 π-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.
Key words
allylic alkylations - amino acids - enolates - peptides - peptide modifications -
palladium
