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 add ition of substituted alkanethiol anions RS- and neutral thiols RSH and thir d-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]cyclo hexa-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 b eta (nuc) = 0.11, which is similar to that for addition of RS- to other hig hly resonance-stabilized carbocations. The rate constants for addition of R S- 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 beta (nuc) = 0.32 for addition df ROH to 5(+) than bet a (nuc) = 0.11 for addition of RS- to 1 shows that there are important diff erences 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 (beta (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 s tate for addition of Me2S to 1 from interactions between the developing cat ionic center at the bulky sulfur nucleophile and the electron-withdrawing a lpha -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 lon g distance and that product destabilizing steric/electrostatic interactions become significant only at smaller C-S bond distances, after the transitio n state has been traversed on the reaction coordinate.