Structure-reactivity relationships for addition of sulfur nucleophiles to electrophilic carbon: Resonance, polarization, and steric/electrostatic effects

Second-order rate constants k(RS) and k(RSH) (M^-1 s^-1) for the direct addition of substituted alkanethiol anions RS^- and neutral thiols RSH and third-order rate constants (k(RSH))(H) (M^-2 s^-1) for acid-catalyzed addition of RSH to the simple quinone methide 4-[bis(trifluoromethyl)methylene]cyclohexa-2,5-dienone (1) in water are reported. Rate and equilibrium constants for the addition of Me₂S and H⁺ to give H-1-SMe₂⁺ were also determined. The data for addition of RS^- to 1 are correlated by the Bronsted coefficient β(nuc) = 0.11, which is similar to that for addition of RS^- to other highly resonance-stabilized carbocations. The rate constants for addition of RS^- to 1 are similar to those for addition of substituted alkyl alcohol ROH to the much more electrophilic 1-(4-methoxyphenyl)ethyl carbocation (5⁺). The larger value of β(nuc) = 0.32 for addition of ROH to 5⁺ than β(nuc) = 0.11 for addition of RS^- to 1 shows that there are important differences in the reaction coordinate profiles for these nucleophile addition reactions, which are discussed. The transition state for addition of RSH to 1 is stabilized by electron-donating alkyl groups R (β(nuc) > 0.5) and by substitution of an electron-donating methyl group for hydrogen at RSH. By contrast, there is relatively little destabilization of the transition state for addition of Me₂S to 1 from interactions between the developing cationic center at the bulky sulfur nucleophile and the electron-withdrawing α-CF₃ groups at 1. The results suggest that C-S bonding interactions in the transition state for addition of Me₂S to 1 develop at a relatively long distance and that product destabilizing steric/electrostatic interactions become significant only at smaller C-S bond distances, after the transition state has been traversed on the reaction coordinate.