Are n-BuLi/TMEDA-mediated arene ortholithiations directed?: Substituent-dependent rates, substituent-independent mechanisms

Rate studies of the lithiation of benzene and related alkoxy-substituted aromatics by n-BuLi/TMEDA mixtures implicate similar mechanisms in which the proton transfers are rate limiting with transition structures of stoichiometry [(n-BuLi)(2)(TMEDA)(2)(Ar-H)]double dagger (Ar-H = benzene, C6H5OCH3, m-C6H4(OCH3)(2), C6H5OCH2OCH3, and C6H5OCH2CH2N(CH3)(2)). Cooperative substituent effects and an apparent importance of inductive effects suggest a mechanism in which alkoxy-lithium interactions are minor or nonexistent in the rate-limiting transition structures. Supported by ab initio calculations, transition structures based upon triple ions of general structure [(n-Bu)(2)Li](-)//Li+(TMEDA)(2) are discussed.