Synthesis of CF3-Azafluorenes through the Cascade Reaction of 2H-Imidazoles with CF3-Ynones.

A concise synthesis of trifluoromethyl (CF3)-substituted azafluorenes based on the reaction of 5-aryl-2H-imidazoles with CF3-ynones is reported. The reaction proceeds through C-H activation-initiated formal [3+2] cycloaddition to give spiro[imidazole-4,1'-indene] as a key intermediate, followed by its retro [3+2] cycloaddition, isomerization, and enamine nucleophilic addition. This synthesis of CF3-azafluorene derivatives via simultaneous formation of both the indene and the pyridine scaffolds through cascade C-H/C-C/C-N bond cleavage and C≡C bond formation has not been disclosed before. Moreover, the products thus obtained showed antiproliferative activity against cancer cell lines.