Hydrophilic BIPHEPHOS Ligand for Pd-Mediated Cysteine Allylation of Peptides and Proteins in Water

The selective and natural post-translational modification of peptides and proteins under biocompatible conditions remains a challenge. Herein, we report a hydrophilic variant of the BIPHEPHOS ligand featuring diethyl phosphonates as solubilizing groups, which were found to be catalytically isofunctional to unpolar <i>tert</i>-butyl. This enabled the fast introduction of native prenyl groups and bioconjugation handles into peptides and folded proteins under nearly aqueous conditions.