Communication Dans Un Congrès Année : 2025

Copper-mediated electrophilic trifluoromethylation of amines

Résumé

The trifluoromethyl group improves the lipophilicity and helps crossing biological barriers. Such properties make it an asset for the activity of drugs, in which the CF3 moiety is, in most cases, bounded to a carbon atom,1 albeit O–CF3 2 and S–CF3 3 linkages can also be found. In contrast, despite the ubiquity of nitrogen atoms in drugs, N–CF3 groups are rarer, notably because of the difficulty to form those bonds. It appears that a direct trifluoromethylation of free amines is difficult.4 Thus, N–CF3 bonds are generally formed by de novo syntheses using the natural nucleophilicity of the nitrogen atom.5,6,7 The incorporation of a CF3 as a whole adduct would require finding a new reactivity. In this work, we used chloramines and their electrophilic nitrogen atoms coupled with a nucleophilic CF3 source to form the N–CF3 bond. The Ruppert-Prakash’s reagent8,9 in the presence of a fluoride source resulted mainly in gaseous CF3Cl. In contrast, an alternative source of nucleophilic CF3, [(phen)CuCF3] (phen = 1,10-Phenanthroline)10 was used and enabled the formation of the desired amine. We then developed a one-pot two-steps synthesis of trifluoromethylamines from free amines in 30 minutes at room temperature using N-chlorosuccinimide (NCS) as the chlorinating agent. The mechanism has also been studied with DFT calculations and electrochemical analyses.

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Dates et versions

hal-05537773 , version 1 (05-03-2026)

Identifiants

  • HAL Id : hal-05537773 , version 1

Citer

Alexandre Touron, Uroš Todorović, Laurent Severy, Thibault Cantat, Emmanuel Nicolas, et al.. Copper-mediated electrophilic trifluoromethylation of amines. SECO 62 - Semaine d'Etudes en Chimie Organique, May 2025, Fournols, France. ⟨hal-05537773⟩
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