Substituent effects on the relative rates and free energies of ortholithiation reactions: Families of fluorobenzenes as the substrates

Abstract

2-, 3- and 4-substituted fluorobenzenes and 5-substituted 1,3-difluorobenzenes were metalated with sec-butyllithium (LIS) and with lithium 2,2,6,6-tetramethylpiperidide (LiTMP) under irreversible conditions in order to determine the rates of reaction relative to the unsubstituted parent compounds (fluorobenzene and 1,3-difluorobenzene). In addition, the pairs of resulting aryllithiums were subjected to acid-base equilibration to furnish the thermodynamic stabilities (or: basicities) of these species again relative to the parent compounds. Not surprisingly, the effect diminishes with the distance of a given substituent to the lithiation center (ortho > para) and it reaches its maximum at the ground state equilibration of the organometallic intermediate whereas it fades away at transition states, in particular reactant-like ones. Fluorine, the most powerful activator in the entire series if located at an ortho position, increases the rates of LIS- and LiTMP-promoted metalations by respectively 2 and 3 powers of ten, but by 7 to 8 powers of ten the aryllithium equilibrium stability.