Effect of Electron-Withdrawing α-Substituents on Nucleophile Selectivity toward 4-Methoxybenzyl Carbocations: Selectivities That Are Independent of Carbocation Stability

Nucleophile selectivities were determined for partitioning of the following 4-MeOC₆H₄CR¹(R²)+ (1-R¹(R²)) between reaction with trifluoroethanol and alkyl alcohols in X/(50-X)/50 (v/v/v) alcohol/trifluoroethanol/water: 1-H(CH₂F); 1-H(CHF₂); 1-CH₃(CF₃); 1-H(CO₂Et); 1-(CF₃)₂. These were combined with selectivities measured in earlier work to give an extended set of data for the reactions of 1-R¹(R²). Destabilization of 1-R¹(R²)⁺ by electron-withdrawing α-substituents leads to a marked increase in nucleophilic selectivity as measured by the rate constant ratio k_MeOH/k_TFE for partitioning between reaction with methanol and trifluoroethanol (1-R¹(R²), k_MeOH/k^TFE): 1-H(CH₃), 41;³ 1-H(CH₂F), 40; 1-H(CHF₂), 44; 1-H(CF₃), 80;4 1-CH₃(CF₃), 94; 1-H(CO₂Et), 115; 1-(CF₃)₂, 180. By contrast, destabilization of α-substituted benzyl carbocations by electron-withdrawing aromatic ring substituents leads to sharp decreases in k_MeOH/k_TFE and in the selectivities for reaction with other nucleophilic reagents.² Two factors are proposed to contribute to the difference in the effects of meta ring substituents and α-substituents on nucleophile selectivity toward benzylic carbocations: (1) differential steric/electrostatic interactions of bulky, electron-withdrawing, α-substituents with electron-donating and electron-withdrawing substituents on the alkyl alcohol, and (2) the tendency of electron-withdrawing α-substituents to cause an increase in the intrinsic reaction barrier which leads to an increase in nucleophile selectivity that offsets the decrease in selectivity due to the changing thermodynamic driving force for the carbocation addition reaction.