Pyrrole groups are found in many bioactive compounds. Modifying them with trifluoromethyl substituents can improve their bioavailability and other properties. While 2-trifluoromethylpyrroles can easily be synthesized, there is a comparative lack of approaches for the synthesis of 3-trifluoromethylpyrroles.
Nicolas Gouault and colleagues, Université de Rennes 1, France, have developed a gold-catalyzed cyclization reaction for the preparation of substituted 3-trifluoromethylpyrroles (example pictured). The team first prepared a range of trifluoromethylated amino propargylic alcohols from commercially available starting materials. Then they mesylated these compounds using mesyl chloride to provide a better leaving group and finally used AuCl as a catalyst for the ring closure that forms the corresponding pyrrole.
The reaction proceeds in good yields and under mild conditions. The approach could also be modified to prepare trifluoromethylated iodopyrroles, which can be used as substrates for cross-coupling reactions to allow further derivatizations.
- Gold-Catalyzed Synthesis of Substituted 3-Trifluoromethylpyrroles from Mesylated Amino Trifluoromethylpropargylic Alcohols,
Benjamin Guieu, Myriam Le Roch, Michèle David, Nicolas Gouault,
J. Org. Chem. 2017.