Cascade Cyclization of Azadienes with Difluoroenoxysilanes: A One-Pot Formal [4 + 2] Approach to Fluorinated Polyfused Heterocycles

A TfOH-promoted synthesis of fluorinated polyfused heterocycles via the cascade cyclization of azadienes and difluoroenoxysilanes has been developed, leading to the facile construction of fluorinated benzofuro[3,2-b]pyridines, 5H-indeno[1,2-b]pyridines, and 5,6-dihydrobenzo[h]quinolines. This one-pot formal [4 + 2] approach involves 1,4-difluoroalkylation, desulfonylation, cyclization, and dehydrated and dehydrofluorinated aromatization and represents the first application of difluoroenoxysilane in cascade transformations. Furthermore, this methodology is highlighted by the synthesis of three fluoro analogues of bioactive molecules with potent topoisomerase inhibitory activities.