Synthesis of optically active trifluoromethyl-substituted 2,3-dihydroimidazo[2,1-b]oxazoles

• CF3-containing β-amino alcohols were used to prepare imidazole N-oxides.
• Fluorinated hydroxyalkyl chain at N(1) enables Ac2O-induced heterocyclization.
• Products were identified as trifluoromethylated imidazo[2,1-b]oxazole.
• The key-intermediate is a highly reactive imidazolium cation.

The 2-unsubstituted imidazole N-oxides with a 3,3,3-trifluoro-2-hydroxypropyl group at N(1) in the presence of acetic anhydride undergo cyclization via the intramolecular nucleophilic attack of the hydroxyl group onto C(2) of the imidazole ring to give trifluoromethylated derivatives of 2,3-dihydroimidazo[2,1-b]oxazoles. This method, starting with enantiopure substrates, allows the preparation of enantiopure products in a one-pot procedure.

Figure optionsDownload as PowerPoint slide