* Rh-catalyzed Trp and Cys alkylation
Using in situ generated Rh-carbenoid by activation of vinyl-substituted diazo compounds with Rh(OAc), tryptophans and cysteines were shown to be selectively alkylated in aqueous media.
However, this method is limited to surface tryptophans and cysteines possibly because of steric constraints.
* Ir-catalyzed Lys and N-terminus (reductive) alkylation
Imines formed from the condensation of aldehydes with lysines or the N-terminus can be reduced efficient by an water-stable [Cp*Ir(bipy)(HO)]SO complex in the presence of formate ions (serving as the hydride source). The reaction happens readily under physiologically relevant conditions and results in high conversion for various aromatic aldehydes.
* Pd-catalyzed Tyr O-alkylation
By using a pre-formed electrophilic π-allylpalladium(II) reagent derived from allylic acetate or carbamate precursors, selective allylic alkylation of tyrosines can be achieved in aqueous solution at room temperature and in the presence of cysteines.
* Au-catalyzed Cys alkylation
Cysteine-containing peptides have been shown to undergo 1,2-addition to allenes in the presence of gold(I) and/or silver(I) salts, producing hydroxyl substituted vinyl thioethers. The reaction with peptides proceeds with high yields and is selective for cysteines over other nucleophilic residues.
However, the reactivity towards proteins is much decreased, potentially due to the coordination of gold to the protein backbone.