Synthesis of Cyanodifluoromethylselenylated Isocoumarins Enabled by a p-CF3BnSe(O)CF₂CN/Tf2O Reagent System

Abstract

p-CF3BnSe(O)CF2CN was developed as a cyanodifluoromethylselenonating reagent. In combination with Tf2O, this reagent system enabled an efficient synthesis of the biologically interesting 4-(cyanodifluoromethylseleno) isocoumarins from 2-alkynylbenzoates. Mechanistically, the transformation was postulated to involve activation of p-CF3BnSe(O)CF2CN by Tf2O to generate an exclusive electrophilic TfO-SeCF2N species, which underwent electrophilic cyanodifluoromethylselenolation and intramolecular lactonization with 2-alkynylbenzoates to afford the corresponding 4-SeCF₂CN isocoumarins.