Twenty-three diarylcarbenium ions and 38 pi-systems (arenes, alkenes, allyl silanes and stannanes, silyl enol ethers, silyl ketene acetals, and enamines) have been defined as basis sets for establishing general reactivity scales for electrophiles and nucleophiles. The rate constants of 209 combinations of these benzhydrylium ions and pi-nucleophiles, 85 of which are first presented in this article, have been subjected to a correlation analysis to determine the electrophilicity parameters E and the nucleophilicity parameters N and s as defined by the equation log k(20 degrees C) = s(N + E) (Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957). Though the reactivity scales thus obtained cover more than 16 orders of magnitude, the individual rate constants are reproduced with a standard deviation of a factor of 1.19 (Table 1). It is shown that the reactivity parameters thus derived from the reactions of diarylcarbenium ions with pi-nucleophiles (Figure 3) are also suitable for characterizing the nucleophilic reactivities of alkynes, metal-pi-complexes, and hydride donors (Table 2) and for characterizing the electrophilic reactivities of heterosubstituted and metal-coordinated carbenium ions (Table 3). The reactivity parameters in Figure 3 are, therefore, recommended for the characterization of any new electrophiles and nucleophiles in the reactivity range covered. The linear correlation between the electrophilicity parameters E of benzhydryl cations and the corresponding substituent constants sigma(+) provides Hammett sigma(+) constants for 10 substituents from -1.19 to -2.11, i.e., in a range with only very few previous entries.

Which electrophiles react with which nucleophiles? The correlation log k(20 degrees Celsius) = s(E + N), in which electrophiles (carbocations, metal-pi-complexes, diazonium ions) are characterized by one (E) and nucleophiles are characterized by two parameters (N, s), proved to be applicable for a wide variety of electrophile-nucleophile combinations. Since the introduction of this correlation in 1994 (Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957), numerous new reagents have been characterized, and in 2001 (J. Am. Chem. Soc. 2001, 123, 9500-9512), a new method of parametrization was proposed that facilitates a continuous extension of the data sets without the need for reparametrization of existing data. This Account adjusts the N and s parameters of all presently characterized pi-nucleophiles (arenes, alkenes, organometallics) to the new parametrization and illustrates how to employ the resulting reactivity scales for analyzing synthetic and mechanistic problems in organic and macromolecular chemistry. Predictions of absolute rate constants, inter- and intramolecular selectivities, and analyses of reaction mechanisms are discussed. We outline how new compounds can be added to the scales and present our view on the scope and limitations of this approach to polar organic reactivity.

In order to quantify the electrophilic reactivities of common Michael acceptors, we measured the kinetics of the reactions of monoacceptor-substituted ethylenes (HC═CH-Acc, 1) and styrenes (PhCH═CH-Acc, 2) with pyridinium ylides 3, sulfonium ylide 4, and sulfonyl-substituted chloromethyl anion 5. Substitution of the 57 measured second-order rate constants (log k) and the previously reported nucleophile-specific parameters N and s for 3-5 into the correlation log k = s(E + N) allowed us to calculate 15 new empirical electrophilicity parameters E for Michael acceptors 1 and 2. The use of the same parameters s, N, and E for these different types of reactions shows that all reactions proceed via a common rate-determining step, the nucleophilic attack of 3-5 at the Michael acceptors with formation of acyclic intermediates, which subsequently cyclize to give tetrahydroindolizines (stepwise 1,3-dipolar cycloadditions with 3) and cyclopropanes (with 4 and 5), respectively. The electrophilicity parameters E thus determined can be used to calculate the rates of the reactions of Michael acceptors 1 and 2 with any nucleophile of known N and s. DFT calculations were performed to confirm the suggested reaction mechanisms and to elucidate the origin of the electrophilic reactivities. While electrophilicities E correlate poorly with the LUMO energies and with Parr's electrophilicity index ω, good correlations were found between the experimentally observed electrophilic reactivities of 44 Michael acceptors and their calculated methyl anion affinities, particularly when solvation by dimethyl sulfoxide was taken into account by applying the SMD continuum solvation model. Because of the large structural variety of Michael acceptors considered for these correlations, which cover a reactivity range of 17 orders of magnitude, we consider the calculation of methyl anion affinities to be the method of choice for a rapid estimate of electrophilic reactivities.

Comprehensive nucleophilicity scales including p-, n-and s-nucleophiles have been constructed using benzhydrylium ions and structurally related quinone methides as reference electrophiles. It is shown how the correlation (Eqn (1)) log k 20-C ¼ s(E R N), where s and N are nucleophile-specific parameters and E is an electrophile-specific parameter, has recently been employed to characterize further classes of nucleophiles (phosphines, amines, isonitriles, trifluoromethanesulfonyl-substituted carbanions) and electrophiles (2-benzylideneindan-1,3-diones and benzylidenebarbituric acids). Practical applications of the reactivity parameters E, N and s for developing Friedel-Crafts alkylations in neutral alcoholic or aqueous solution and for characterizing nucleophilic organocatalysts will be discussed. Eventually, a new correlation equation will be presented, which includes Eqn (1), the Ritchie equation (nucleophilic additions to stabilized carbocations), and the Swain-Scott equation (nucleophilic substitutions of methyl halides) as special cases. Figure 4. The benzhydrylium scale: Basis for a quantitative model of polar organic reactivity Figure 5. Fit of second-order rate constants for electrophile nucleophile combinations (20 8C) to Eqn (1)

The concept of hard and soft acids and bases (HSAB) proved to be useful for rationalizing stability constants of metal complexes. Its application to organic reactions, particularly ambident reactivity, has led to exotic blossoms. By attempting to rationalize all the observed regioselectivities by favorable soft-soft and hard-hard as well as unfavorable hard-soft interactions, older treatments of ambident reactivity, which correctly differentiated between thermodynamic and kinetic control as well as between different coordination states of ionic substrates, have been replaced. By ignoring conflicting experimental results and even referring to untraceable experimental data, the HSAB treatment of ambident reactivity has gained undeserved popularity. In this Review we demonstrate that the HSAB as well as the related Klopman-Salem model do not even correctly predict the behavior of the prototypes of ambident nucleophiles and, therefore, are rather misleading instead of useful guides. An alternative treatment of ambident reactivity based on Marcus theory will be presented.

The reactivity-selectivity principle (RSP), once a tenet of organic chemistry, eroded during the 1970s and was more or less abandoned by 1980. Although it has been clear for more than 25 years that a decrease in selectivity with increasing reactivity can only be expected with certainty if diffusion control is approached, the RSP has survived as an intuitively appealing rule. This Minireview shows why selectivity cannot generally decrease with increasing reactivity and highlights the weaknesses of the theoretical foundations of the RSP.

Rates of hydride transfer from several hydride donors to benzhydrylium ions have been measured at 20 °C and used for the determination of empirical nucleophilicity parameters N and s(N) according to the linear free energy relationship log k(20 °C) = s(N)(N+E). Comparison of the rate constants of hydride abstraction by tritylium ions with those calculated from the reactivity parameters s(N), N, and E showed fair agreement. Therefore, it was possible to convert the large number of literature data on hydride abstraction by tritylium ions into N and s(N) parameters for the corresponding hydride donors, and construct a reactivity scale for hydride donors covering more than 20 orders of magnitude.

The kinetics of the reactions of benzhydryl cations with 22 enamines, three pyrroles, and three indoles were investigated photometrically in dichloromethane. The nucleophilicity parameters N and slope parameters s of these electron-rich pi-systems were derived from equation log k (20 degrees C)=s(E+N) and compared with the nucleophilicities of other pi-systems (silyl enol ethers, silyl ketene acetals) and carbanions. It is shown that the nucleophilic reactivities of enamines cover more than ten orders of magnitude, comparable to enol ethers on the low reactivity end and to carbanions on the high reactivity end. Since the products of N-attack are thermodynamically less stable than the reactants, the observed rate constants refer to the formation of the carbon bond;carbon bonds. In some cases, equilibrium constants for the formation of iminium ions were measured, which allow one to determine the intrinsic rate constants of these reactions.