Synthesis of CF<sub>3</sub>-Azafluorenes through the Cascade Reaction of 2<i>H</i>-Imidazoles with CF<sub>3</sub>-Ynones
Hao Li, Shengnan Yan, Chunhua Ma, Xinying Zhang, Xuesen Fan
Abstract
A concise synthesis of trifluoromethyl (CF 3 )-substituted azafluorenes based on the reaction of 5-aryl-2 H -imidazoles with CF 3 -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 CF 3 -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.