2,2,2-Trifluoroethanol as a solvent to control nucleophilic peptide arylationElectronic supplementary information (ESI) available. See DOI: 10.1039/c7ob00295e.Underlying research data for this paper is available in accordance with the EPSRC open data policy from DOI: 10.15128/r29880vq960

The S N Ar arylation of peptides with perfluoroaromatics provides a route by which to install a useful chemical handle that enables both 19 F-NMR analysis and further chemical modification. However, chemo-selective arylation in peptides containing multiple nucleophilic side chains currently presents a challenge to the field. Herein, we demonstrate that employing 2,2,2-trifluoroethanol (TFE) as a solvent in peptide S N Ar reactions significantly improves nucleophile-selectivity when compared to N , N ′-dimethylformamide (DMF). Trifluoroethanol enables selective perfluoro-heteroaromatic peptide arylation of cysteine residues.