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 Me 2 S and H + to give H-1-SMe 2 + were also determined. The data for addition of RS - to 1 are correlated by the Brønsted 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 Me 2 S to 1 from interactions between the developing cationic center at the bulky sulfur nucleophile and the electron-withdrawing α-CF 3 groups at 1 . The results suggest that C−S bonding interactions in the transition state for addition of Me 2 S 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.