The Mechanism of Lithium Zincate-Mediated I/Zn Exchange Revisited: A Computational Micro-Solvation Approach in THF

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. Four mechanistic pathways have been calculated, including a literature-inspired pathway with preservation of the synergic character of the reagent (pathway 1), an OMs-directed I/Zn exchange pathway (pathway 2), a THF-solvated open complex-promoted pathway (pathway 3) and an anionic pathway (pathway 4). While pathway 4 could be fully precluded, pathway 3 turned out to be the most energetically favoured. Equivalent thermodynamic profiles were found for both pathways 1 and 2, albeit a slight preference can be attributed to the latter 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.