The first fluoroalkylation of amino acids and peptides in water utilizing the novel iodonium salt (CF₃SO₂)₂NI(Ph)CH₂CF₃

Abstract

The novel iodonium salt (CF₃SO₂)₂NI(Ph)CH₂CF₃ is a powerful alkylating reagent which can be utilized in water to trifluoroethylate amino acids and peptides.

References

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12. S-CF₃CH₂-FMOC-L-Cys-F was reacted with (–)-(S)-phenethylamine in water–NaHCO₃–CH₂Cl₂.¹⁰ The same reaction was carried out on S-CF₃CH₂-Fmoc-(D,L)-Cys-F, prepared from racemic cysteine. S-CF₃CH₂-Fmoc-L-Cys-NHCHMePh was a single product by ¹H and ¹⁹F NMR. S-CF₃CH₂-Fmoc-(D,L)-Cys-NHCHMePh was clearly a 1∶1 mixture of two compounds [δ_F(CHCl₃–CFCl₃)–66.99, –67.00]. Because the starting material for 6 is only available in the L form, 6 was converted into N^ε(CF₃CH₂)₂-N^α-Fmoc-L-Lys-F, which was reacted separately with (–)-(S)- and (+)-(R)-phenethylamine. Each amide was identified by NMR. Equal amounts of the two amides were combined, and the mixture showed two compounds by both ¹H and ¹⁹F NMR [δ_F(CHCl₃–CFCl₃)–70.83, –70.86].
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14. Ms J. Sayers, NSF-SURP 1997, obtained from 4-aminobutyric acid (GABA) and 1 under the same simple conditions (CF₃CH₂)₂N(CH₂)₃CO₂CH₂CF₃ in very high yield (NMR). A nonvolatile, easily isolated analog was obtained from GABA phenylethyl ester hydrochloride. The yield of (CF₃CH₂)₂N(CH₂)₃CO₂C₂H₄Ph was 70%, representing more than 80% per alkylation step: D. D. DesMarteau, J. Sayers and V. Montanari, manuscript in preparation.