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Thème de recherche

Fluorinated amino acids

Since long time we devoted to the reactivity of aldimine derivatives derived from fluoral which allowed an easy access to particularly interesting motifs as peptidomimetic units. Here are some examples :

  • First example of an asymmetric aza-Baylis–Hillman reaction involving a CF3-sulfinylimine as an electrophile (Coll. with the Pr. V. Soloshonok, Spain).
    Eur. J. Org. Chem. 2014, 3072.
  • Asymmetric synthesis of CF3‐β‐proline and CF3‐6‐membered cyclic amino acids from readily available N‐tert‐butanesulfinyl‐(3,3,3)‐trifluoroacetaldimine.
    Eur J. Org. Chem., 2018, 3688-3692

New N-fluoroalkyl synthons

Very recently we have been interested in other scaffolds where the fluorinated group is present directly on the nitrogen atom. Unlike the O-Rf (for example O-CF3) and S-Rf (SCF3) motifs, the N-CF2R motif is very poorly studied. These N-Rf patterns only begin to appear very recently. On the other hand, peptidomimetic units possessing these motifs have not yet been exploited.

  • The few approaches to accessing N-Rf patterns.
    These methods generally use the reaction of fluoride ions on N-CS2R or the fluoride / halogen exchange on N-CCl3, or the electrophilic trifluoromethylation reaction with amines. These different approaches make it possible to access almost exclusively the N-CF3 motif, and generally on very little functionalized molecules. In the case of the NCF2H group, the synthesis is more developed in the literature from different reagents (HCClF2, CF3CO2R, XCF2CO2R, RSO2CF2CO2R, TMSCF2Br, TMSCF3 ...) which generally involves the formation of CF2 carbene). However there is no approach for the synthesis of functionalized N-Rf (NCF2R, NCF2COR, NCF2CO2R ...). The synthesis of these new compounds will allow to better know their physicochemical properties and thus to exploit them at best in several fields.
    Review in C. R. chimie 2018, 21, 771.
  • Addition of nucleophilic fluorinated groups on electrophilic nitrogens.
    The azodicarboxylate derivatives were the first reagents to be used. The CF3, CF2COR and CF2CO2Et groups were added to the azodicarboxylate compounds.
    J. Org. Chem. 2015, 80, 1964

N-difluoromethylated triazoles

Synthesis and incorporation of N-difluoromethylated triazoles into peptides.
We have developed a simple, efficient, direct approach to prepare N-difluoromethylated pseudopeptides.
NMR and X-rays analysis show intramolecular H-F interactions of fluorine atoms with hydrogens of amides and triazole. These non-negligible interactions make the structure constrained, and maintain the peptide in an extended conformation
Chem. Commun. 2017, 56, 5024