Developing an Ionic Halide Transfer and Addition Process Driven by Theoretical and Experimental Synergy

By combining theoretical and experimental approaches, a novel ionic alternative to the atom transfer radical addition (ATRA) reaction has been developed. Based on the halogenophilic nucleophilic substitution (S_N2X) process, this new base-mediated protocol termed halide transfer and addition (HTA) enables the concurrent formation of C(sp³)-C(sp³) and C(sp³)-X bonds from α-halo carbonyls and electron-deficient alkenes. DFT modeling elucidated the importance of 1,4-dioxane in dissociating the KO^<i>t</i>Bu tetramer for reaction initiation and coordination. The K⁺ cation is stabilized by the solvent and can direct reaction progression, leaving the ^<i>t</i>BuO^- anion free to drive the S_N2X, supporting a detailed mechanistic proposal for the HTA process. Experimental studies were conducted to verify theoretical predictions, scope the reactivity, and iteratively improve both the model and mechanistic insight, resulting in a synergistic optimization loop for synthetic chemistry reaction method development.