Catalytic Phosphorylation of Tyrosine via a Radical Arbuzov Reaction

Synthetic protein/peptide modification is a powerful strategy for the development of new therapeutics and tools for chemical biology. Accordingly, the development of a synthetic variant of biological tyrosine phosphorylation, a cornerstone of the post-translational modification landscape, could find widespread application in the study of this fundamental biochemical signal. This work describes the development of a mechanistically-novel, redox-neutral, photocatalytic tyrosine phosphorylation reaction via a radical Arbuzov-type mechanism. The reaction proceeds with good tyrosine selectivity in di-, tri- and oligopeptides under mild conditions near neutral pH, tolerating potentially problematic functionality. As the first photocatalytic tyrosine phosphorylation reaction, this work represents a major advance towards the goal of synthetic tyrosine phosphorylation.