The Mechanism of Lithium Zincate‐Mediated I/Zn Exchange Revisited: A Computational Microsolvation Approach in THF**

Abstract

Lithium trialkylzincate‐mediated I/Zn exchange reaction has been revisited computationally through a micro‐solvation approach. A never yet investigated iodoaryl derivative bearing a potential bulky para‐directing group, namely 4‐iodobenzyl mesylate, was considered as a substrate. THF as typical solvent and Et3ZnLi have also been considered for the first time in such a reaction. Three mechanistic pathways have been calculated, including (1) a literature‐inspired pathway with full preservation of the synergic character of the reagent as well as a complementary mesylate group‐directed pathway, (2) a THF‐solvated open complex‐promoted pathway and (3) an anionic pathway. While the anionic pathway appeared to be unlikely, pathway involving a THF‐solvated open zincate complex turned out to be the most energetically favoured. Equivalent thermodynamic profiles were found for both complementary pathways with preservation of the synergic character of the reagent, albeit a slight preference could be attributed to that occurring with initial chelation of Li to the mesylate group (OMs) through micro‐solvation approach. The I/Zn exchange was shown to proceed through a lithium‐assisted aryl shuttle‐like process. The iodoaryl substrate is first converted into ArLi intermediate which in turns reacts with the remaining diorganozinc reagent.