Deprotonative Metalation of Methoxy-Substituted Arenes Using Lithium 2,2,6,6-Tetramethylpiperidide: Experimental and Computational Study

The reaction pathways of lithium 2,2,6,6-tetramethylpiperidide (LiTMP)-mediated deprotonative metalation of methoxy-substituted arenes were investigated. Importantly, it was experimentally observed that, whereas TMEDA has no effect on the course of the reactions, the presence of more than the stoichiometric amount of LiCl is deleterious, in particular without an in situ trap. These effects were corroborated by the DFT calculations. The reaction mechanisms, such as the structure of the active species in the deprotonation event, the reaction pathways by each postulated LiTMP complex, the stabilization effects by in situ trapping using zinc species, and some kinetic interpretation, are discussed herein