Site-specific chemical modification of peptides and proteins is becoming increasingly important in research and industry for monitoring cellular events or designing therapeutics, targeting ligands and molecular probes. 1 However the number of chemical transformations that are suitable for efficient biomolecule functionalization is limited by the stringent conditions required (mild and aqueous conditions, high selectivity, low toxicity) and developing chemo-and siteselective transformations remains a prominent challenge. Traditional methods for bioconjugation target nucleophilic lysine and cysteine residues (Scheme 1a). 2 However, functionalization of the abundant lysine tends to lack selectivity. Modification of the rarer cysteine often requires cleavage of disulfide bonds, which play an important role in the folding and stability of proteins, or the expression of non-natural proteins with selectively introduced cysteines. To overcome these limitations and expand the functionalization toolbox, less exploited amino acids such as methionine, 4 tryptophan, 5 histidine 6 and tyrosine have been investigated. Tyrosine bioconjugation in particular shows promising results (Scheme 1b). Among natural amino acids, it is an interesting residue for site-selective modification, as it is relatively rare on protein surfaces, and is often buried within the protein structure due to the amphiphilicity of the phenol moiety. Several elegant methods have been reported for C-modification of tyrosine, such as three-component Mannich-type reactions, or reactions with aryldiazonium salts, 10 diazodicarboxamides 11 and radicals. O-functionalization has also been described, with for example reaction with electrophilic π-allyl palladium complexes, SuFEx reagents 14 and glycosylation reactions. Functionalization has also been achieved via dearomatization-rearomatization strategies, or formation of a rhodium arene complex. All these strategies have advantages, but also inherent limitations, and therefore the development of alternative methods is still highly desirable.