Structure−Reactivity Relationships for Addition of Sulfur Nucleophiles to Electrophilic Carbon: Resonance, Polarization, and Steric/Electrostatic Effects

Abstract

Second-order rate constants kRS and kRSH (M-1 s-1) for the direct addition of substituted alkanethiol anions RS- and neutral thiols RSH and third-order rate constants (kRSH)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 Brønsted coefficient βnuc = 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 βnuc = 0.32 for addition of ROH to 5+ than βnuc = 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 (βnuc > 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.