PREDICTING DIRECTED LITHIATIONS BY MEANS OF MNDO-DETERMINED AGOSTIC INTERACTION PARAMETERS AND PROXIMITY FEATURES - PERI LITHIATION OF POLYHYDRIC PHENOLIC-COMPOUNDS

The feasibility of the direct lithiation of monohydric compounds (such asa secondary benzamide, phenol, and thiophenol) and dihydric and tri hydric phenols has been theoretically examined by using the semiempiri cal MNDO method. MNDO-determined agostic interaction parameters and pr oximity features show an outstanding capacity in qualitatively predict ing the closeness of the corresponding transition states. According to these parameters, peri lithiation of mono- or polyhydric phenolic com pounds (whenever possible) should be kinetically favored over alternat ive processes. Even second peri lithiations appear to be achievable ob jectives on account of these indicators. These prognostications have b een borne out by experiment for the first time as dihydric phenols of the naphthalene, anthracene, and phenanthrene series yielded peri-subs tituted products on treatment with nBuLi in N,N,N',N'-tetramethylethyl enediamine (TMEDA) as solvent, followed by quenching with common elect rophiles. Double peri functionalized derivatives of several dihydroxyn aphthalenes and phenanthrenes were obtained by directed lithiation of the unprotected compounds. These results strongly suggest the key role that agostic interaction plays on directed lithiations and provide in direct evidence for the intermediacy of such precoordinated species in these reactions.