Scope and Mechanistic Limitations of a Sonogashira Coupling Reaction on an Imidazole Backbone

Abstract

A Sonogashira coupling reaction method to join terminal alkynes to the imidazole backbone was developed and investigated. The method exhibits good functional group tolerance and provides target 4-alkynylated imidazoles in 70-93% yield. The alkyne reagents were characterized by means of DFT calculations, from which electrostatic potential surfaces (EPS) were produced. A clear correlation between the EPS of the triple bond and the success of the coupling reaction was revealed. If the EPS is in range -94 to -105 kJmol-1 the coupling is successful. An unsuccessful class of reagents (alkynols) was made compatible by means of an auxiliary group (tert-butyldimethylsilyl). EPSs of these modified reagents then resembled those of the model and these auxiliary-assisted reagents then coupled successfully in excellent yields.