An HF and DFT ab initio Study on the Mechanism of ortho-Directed Lithiation of Hydric and Nonhydric Aromatic Compounds Incorporating Aggregation and Discrete Solvation: The Role of N,N,N′,N′-Tetramethylethane-1,2-diamine (TMEDA) in Lithiation Reactions

Abstract

An HF and DFT ab initio study was set up to decipher the roles of aggregation and solvation in the ortho-directed lithiation of aromatics (hydric and nonhydric), as well as to shed light on the much debated question of precomplexation in the mechanism of lithiation. Ab initio (HF/6-31-G*) calculations on the lithiation of non-hydric aromatics have uncovered several competitive routes operating as a function of the aggregation state of the organolithium base used. Specifically, two competitive routes were found for the lithiation of the anisole model 2 by organolithium dimers 1-dim, namely the so-called cyclic-dimer and open-dimer routes, whereas, for organolithium tetramers 1-tet, the corresponding cyclic route is the only one operative, and, for monomers 1-mon, several optional routes seem to be available. Precomplexation is, in all cases, a requirement. According to the computational data presented, the mysterious rate acceleration experimentally observed for lithiations carried out in TMEDA can be assigned to an aggregation effect on the intermediate open-dimer species, which subsidiarily give rise to several so-called s-monomer routes, of which the dimerization-driven s-monomer route s-m3b is the one having the lowest energy barrier. The relevant species characteristic of both the open-dimer and s-monomer routes are the so-called open dimers, i.e., high-energy intermediates (actually, spiro dimeric aggregates), resulting from cleavage-induced associative complexation of the aromatic substrate upon the fully solvated organolithium dimer. DFT calculations (B3LYP/6-31+G*) also revealed that the peri-lithiation (i.e., Li at C(8)) of 1-naphthol model 3 is a slow process taking place preferentially through the open-dimer route.