Zn(II) Byproduct Enhances the Cu-Catalyzed Cross-Coupling of Bromozinc Difluorophosphonate with Iodobenzoates: A DFT Study

The copper-catalyzed cross-coupling of bromozinc difluorophosphonate with iodobenzoates has been studied with the DFT methodology in order to understand the experimentally observed reactivity. The directing carboxylate group promotes the reaction for methyl 2-iodobenzoate and, unexpectedly, also for methyl 4-iodobenzoate, although to a lesser extent. DFT calculations show that the Zn­(II) byproduct, formed in the initial stages of the reaction, remains attached to the catalyst and serves as an anchoring point for the benzoate moiety, allowing in turn the reaction for both ortho- and para-substituted iodobenzoates. The computationally derived reaction mechanism has also been applied to study whether other substrates may engage in a similar cross-coupling process with bromozinc difluorophosphonate. The calculations carried out on substrates bearing nitrogen-directing groups, such as triazene and pyridine, indicate that their reactions should be possible and that the latter should produce a much faster reaction in comparison to iodobenzoates.