Rate enhancing and rate retarding effects of methoxy substituents on arene metalation

Competition expts. have been performed to det. the rates, relative to benzene, with which anisole, the three dimethoxybenzenes and the three trimethoxybenzenes are deprotonated by sec-butyllithium. Only the first substituent (anisole relative to benzene) has a strong effect (krelf 2800); the second one accelerates moderately at best (1,3-dimethoxybenzene relative to anisole: krelf 12). Methoxy groups being located para with respect to the metalation site or occupying a vicinal position to another methoxy substituent diminish the reactivity by up to two powers of ten (relative to anisole). These surprising findings are without precedence. [on SciFinder (R)]