Enantiopure 5-CF-Proline: Synthesis, Incorporation in Peptides, and Tuning of the Peptide Bond Geometry.

The straightforward synthesis of enantiopure 5-()-and 5-()-trifluoromethylproline is reported. The key steps are a Ruppert-Prakash reagent addition on l-pyroglutamic esters followed by an elimination reaction and a selective reduction. The solution-phase and solid-phase incorporation of this unprotected enantiopure fluorinated amino acid in a short peptide chain was demonstrated.