Synthesis of Perfluoro-tert-butyl Tyrosine, for Application in 19F NMR, via a Diazonium-Coupling Reaction

This is the authors' abstract. We don't add key points for this paper.

A practical synthesis of the novel highly fluorinated amino acid Fmoc-perfluoro- tert -butyl tyrosine was developed. The sequence proceeds in two steps from commercially available Fmoc-4-NH 2 -phenylalanine via diazotization followed by diazonium coupling reaction with perfluoro- tert -butanol. In peptides, perfluoro- tert -butyl tyrosine was detected in 30 s by NMR spectroscopy at 500 nM peptide concentration due to nine chemically equivalent fluorines that are a sharp singlet by 19 F NMR. Perfluoro- tert -butyl ether has an estimated σ p Hammett substituent constant of +0.30.