Copper-Catalyzed Annulative Synthesis of 2-Fluoromethylated Quinolines

Significance

Reported is the synthesis of 2-fluoromethylated quinolines through a copper-catalyzed cyclization of N-aryl-fluorinated imidoyl iodides with terminal alkynes. The reaction proceeds in modest to excellent yields and tolerates ortho-, meta- and para-substitution on the aryl component, although meta-substitution leads to a mixture of products. The presence of the α-H on the terminal alkyne was found to be integral for the success of this reaction. When non-fluorinated alkynylimines were used as starting materials, pyrrole products were formed. This is possibly due to the strong electron-withdrawing effect of the fluorines, whereby the electron density and nucleophilicity of nitrogen is greatly reduced. Based on above discoveries, a mechanism involving allene intermediates was proposed.