A New and Convenient Synthesis ofS-Trifluoromethyl-Containing Amino Acids

Electrophilic S‐Trifluoromethylation of Cysteine Side Chains in α‐ and β‐Peptides: Isolation of Trifluoro‐methylated Sandostatin® (Octreotide) Derivatives

“…If the trifluoromethylation of such surface SH groups in proteins and enzymes were possible (Scheme 6), without drastically altering their physiological properties, three important applications could be envisioned. i) The CF 3 group will provide a unique identification of the species by 19 F-NMR spectroscopy; there is no interference of 19 F-resonance with any other magnetic nucleus in the molecule, which would allow facile NMR imaging in cells, in tissues, and in plants or animals.…”

“…Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2-position). The products are purified by chromatography, and identified by 1 H-, 13 C-, and 19 F-NMR spectroscopy, by CD spectroscopy, and by high-resolution mass spectrometry. The CF 3 groups, thus introduced, may be replaced by H (Na/NH 3 ), an overall Cys/Ala conversion.…”

“…The hitherto less common electrophilic S-trifluoromethylation with (trifluoromethyl)dibenzothio-, -seleno-, or -tellurophenium salts (Umemoto and Ishihara [17]) requires preformed sodium thiolates, and the product is accompanied by a considerable amount of disulfide. In particular, for the direct preparation of S-(trifluoromethyl)-cysteine derivatives, reaction conditions involving t-BuO 2 H [15] [18] or liquid NH 3 [19] had to be employed. In contrast, with reagent A essentially no disulfide by-product is formed.…”

Mild Electrophilic Trifluoromethylation of Carbon‐ and Sulfur‐Centered Nucleophiles by a Hypervalent Iodine(III)–CF3 Reagent

“…We are aware of only very few pyranose derivatives bearing a SCF 3 moiety that are comparable to product S12 16. Previous methods for the direct preparation of S ‐trifluoromethyl‐ L ‐cysteine derivatives required reaction conditions involving t BuOOH17 or liquid ammonia 18. However, with compound 1 the S trifluoromethylation of simple cysteine esters in either the N‐protected or the unprotected form can be carried out in high yield under very mild conditions.…”

Site‐Selective Trifluoromethylation Reactions of Oligopeptides

“…In particular, the substantial nucleophilic character of the thiol motif renders Cys unit an ideal platform for targeted functionalization . Early examples on the S ‐trifluoromethylation of a Cys residue are traced back to 90s, when Soloshonok and Langlois independently utilized CF 3 I in liquid ammonia under ultraviolet irradiation and CF 3 SO 2 Na in combination with tert ‐butyl hydroperoxide (TBHP), respectively, for the assembly of simple trifluoromethylated Cys amino acids. Innovation aside, the latter suffered from serious downsides in terms of operational practicality, and they were only applied to a limited number of simple systems.…”