Electrochemically Driven, p K a -Controlled Regioselective Selenocyclization: Synthesis of Isocoumarin-1-imines with Structural Validation

This study presents an electrochemical strategy that leverages the pKa of N-substituents to achieve precise regiocontrol in the selenocyclization of 2-alkynylbenzamides, providing efficient access to 4-selenyl isocoumarin-1-imines. This method successfully overcomes the longstanding selectivity challenges between competitive O/N-attack cyclization pathways. Crucially, the structure of the O-cyclized product was unambiguously confirmed by X-ray crystallographic analysis. Density functional theory (DFT) calculations further rationalize the observed high regioselectivity, revealing a significantly lower energy barrier for the O-attack pathway. The gram-scale synthesis and preliminary bioassays for fungicidal activity demonstrate the potential applications of this method.