Kinetics of the reactions of enamines and carbanions with commonly used fluorinating reagents, N-fluorobenzenesulfonimide (NFSI), N-fluoropyridinium salts, Selectfluor, and an N-fluorinated cinchona alkaloid, have been investigated in acetonitrile. The reactions follow second-order kinetics, and from the measured rate constants one can derive that the fluorinations proceed via direct attack of the nucleophiles at fluorine, not by SET processes. Correlations of the fluorination rates with the p K values of the nucleofugal leaving groups and the calculated fluorine plus detachment energies are discussed. The rate constants for the reactions with deoxybenzoin-derived enamines follow the linear free energy relationship log k(20 °C) = s( N + E) which allows the empirical electrophilicity parameters E for these fluorinating agents to be derived from the measured rate constants and the tabulated N and s parameters for the nucleophiles. Though the deviations of the measured rate constants from those calculated by this relationship are larger than for reactions of C-centered electrophiles with nucleophiles, it is shown that the electrophilicity parameters E reported in this work are able to rationalize known fluorination reactions and are, therefore, recommended as guide for designing new electrophilic fluorinations.

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 (Δ G°). Often, little attention is paid to the fact that structural effects on ΔG are composed of a thermodynamic (Δ G°) and a truly kinetic (intrinsic) component (ΔG ), as expressed by the Marcus equation. Rate and equilibrium constants have been determined for a number of reactions of enamines with benzhydrylium ions (Aryl CH ), 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 π 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)NR , which have been designed as reference nucleophiles for the future quantification of electrophilic reactivities, are explicitly described.

The kinetics of the reactions of trimethylsilyl enol ethers and enamines (derived from deoxybenzoin, indane-1-one, and α-tetralone) with reference electrophiles (p-quinone methides, benzhydrylium and indolylbenzylium ions) were measured by conventional and stopped-flow photometry in acetonitrile at 20 °C. The resulting second-order rate constants were subjected to a least-squares minimization based on the correlation equation lg k = s N(N + E) for determining the reactivity descriptors N and s N of the silyl enol ethers and enamines. The relative reactivities of structurally analogous silyl enol ethers, enamines, and enolate anions towards carbon-centered electrophiles are determined as 1, 107, and 1014, respectively. A survey of synthetic applications of enolate ions and their synthetic equivalents shows that their behavior can be properly described by their nucleophilicity parameters, which therefore can be used for designing novel synthetic transformations.

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A pallette of commonly used directing groups, including various pharmaceutically relevant nitrogen-containing heterocycles, are quantitatively ranked based on the results of intermolecular hydrogen isotope exchange competition reactions using two iridium...