Which Factors Control the Nucleophilic Reactivities of Enamines?

Changes in rate constants, equivalent to changes in Gibbs energies of activation ΔG≠, are commonly referred to as kinetic effects and differentiated from thermodynamic effects (ΔrG°). Often, little attention is paid to the fact that structural effects on ΔG≠ are composed of a thermodynamic (ΔrG°) and a truly kinetic (intrinsic) component (ΔG0≠), as expressed by the Marcus equation. Rate and equilibrium constants have been determined for a number of reactions of enamines with benzhydrylium ions (Aryl2CH+), which has allowed the determination of Marcus intrinsic barriers and a differentiated analysis of structure–reactivity relationships. To our knowledge, this is the first report in which the Lewis basicity of a πCC bond towards carbon‐centered Lewis acids (for example, carbenium ions) has quantitatively been determined. The synthesis, structures, and properties of deoxybenzoin‐derived enamines ArCH=C(Ph)NR2, which have been designed as reference nucleophiles for the future quantification of electrophilic reactivities, are explicitly described. Strong Lewis bases but weak nucleophiles: The nucleophilicities (N) and Lewis basicities of deoxybenzoin‐derived enamines have been determined in order to employ them in the characterization of colorless electrophiles. High intrinsic barriers are responsible for the observation that enamines are much weaker nucleophiles than pyridines and tertiary amines despite their comparable Lewis basicities (see figure).