Quantitative Predictions of Substituent and Solvent Effects on the Regioselectivities of Nitrile Oxide Cycloadditions to Electron-Deficient Alkynes

Hybrid density functional theory calculations with the B3LYP/6-31G∗ method were used to calculate the activation barriers of nitrile oxide cycloadditions to the unsymmetrical alkynes cyanoacetylene and methyl propiolate. Inherent electronic effects and solvent polarity both influence regioselectivity.