The concept of 1,3‐dipolar cycloadditions was presented by Rolf Huisgen 60 years ago. Previously unknown reactive intermediates, for example azomethine ylides, were introduced to organic chemistry and the (3+2) cycloadditions of 1,3‐dipoles to multiple‐bond systems (Huisgen reaction) developed into one of the most versatile synthetic methods in heterocyclic chemistry. In this Review, we present the history of this research area, highlight important older reports, and describe the evolution and further development of the concept. The most important mechanistic and synthetic results are discussed. Quantum‐mechanical calculations support the concerted mechanism always favored by R. Huisgen; however, in extreme cases intermediates may be involved. The impact of 1,3‐dipolar cycloadditions on the click chemistry concept of K. B. Sharpless will also be discussed.

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.

One for all? The nucleophilicity parameters N, which have been derived from the rate constants k of reactions of nucleophiles with carbocations, also hold for SN2‐type reactions (see scheme). A general equation is suggested which includes established correlations (Swain–Scott, Ritchie) as special cases.

Dedicated to Professor Dieter Enders on the occasion of his 65th birthdaySince the first isolation and characterization of stable Nheterocyclic carbenes (NHCs) by Arduengo and co-workers in 1991, [1] these compounds have attracted great interest in various fields of chemistry. As molecules with divalent carbon atoms, NHCs (e.g., 1-3, Scheme 1) are not only of theoretical interest [2] but also of practical relevance as ligands in metal complexes [3] and as nucleophilic organocatalysts.[4]Despite the extensive use of NHCs as organocatalysts, quantitative investigations of their catalytic activities are rare.[5] Since the relative reactivities of different nucleophiles towards electrophiles correlate only poorly [6] with the corresponding Brønsted basicities (pK aH ), [7] we have recently employed benzhydrylium ions and structurally related quinone methides 4 (Table 1) with widely varying reactivities as reference compounds [8] to compare the nucleophilicities and Lewis basicities of various organocatalysts. [9] It was demonstrated that the rates of the reactions of carbocations and Michael acceptors with n-, p-, and snucleophiles can be described by the linear free-energy relationship in Equation (1), where electrophiles are charac-terized by one solvent-independent electrophilicity parameter E, and nucleophiles are characterized by two solventdependent parameters, the nucleophilicity parameter N, and a nucleophile-specific sensitivity parameter s N .[8]We now report on the use of the benzhydrylium methodology for characterizing the nucleophilicities of three representative NHCs (1 d, 2 d, and 3 e) and for comparing them with other nucleophilic organocatalysts.Representative combinations of the carbenes 1 d, 2 d, and 3 e with the reference electrophiles 4 a or 4 i showed the course of the reactions (Scheme 2). The products formed from 1 d and 2 d and the quinone methide 4 i in THF were subsequently treated with one equivalent of HBF 4 to generate the salts 5 a,b, which were isolated and characterized as described in the Supporting Information. Addition of the Enders carbene 3 e to the blue solution of the benzhydrylium tetrafluoroborate 4 a-BF 4 in THF at ambient temperature led to decolorization and formation of the adduct 5 c, which has been isolated and characterized by X-ray crystallography.

Noncovalent interactions like halogen, chalcogen, and pnictogen bonding are known for a very long time. During the last decade, these interactions have found different applications in catalysis. These forces are often called σ‐hole interactions which can be explained by the anisotropic distribution of the electron density around these atoms. In this MiniReview, we will present recent applications of halogen, chalcogen, and pnictogen bonding in catalysis and discuss experimental and computational investigations to gain more insights into the underlying mechanisms.

Molecular iodine is an excellent catalyst for many organic transformations, but the origin of its catalytic activity is still unknown. To answer this question, we have analyzed four iodine-catalyzed reactions by density functional theory. Our calculations reveal that molecular iodine significantly reduces the activation free energies (−7.6 < ΔG ⧧ < –1.8 kcal mol–1) for reactions involving α,β-unsaturated carbonyls or nitrostyrenes. Closer analysis of the nature of the interaction between iodine and the corresponding Michael acceptors suggests that halogen bonding is the origin of the catalytic activity. The computational and experimental studies show that hidden Brønsted acid catalysis as a competing pathway due to the formation of hydrogen iodide via hypoiodites in aprotic solvents seems less likely for these reactions.

Molecular iodine has been used for more than 100 years as a remarkable catalyst for many organic transformations such as cycloadditions, Michael and aldol reactions, or esterifications. Different explanations for the origin of its catalytic effect have been proposed in the last decades including a "hidden" Brønsted acid catalysis by HI, a Lewis-acid (or halogen-bond) activation, or catalysis by an iodonium(I) species. Recently, iodine catalysis again gained more interest due to the latest developments in halogen-bond catalysis. In this Minireview, we first summarize the experimental basis for the proposed modes of activation. Subsequently, we analyze typical iodine-catalyzed reactions to gain more insights into the underlying reaction mechanisms.

The kinetics of the reactions of the ambident 2- and 4-pyridone anions with benzhydrylium ions (diarylcarbenium ions) and structurally related Michael acceptors have been studied in DMSO, CH(3)CN, and water. No significant changes of the rate constants were found when the counterion was varied (Li(+), K(+), NBu(4)(+)) or the solvent was changed from DMSO to CH(3)CN, whereas a large decrease of nucleophilicity was observed in aqueous solution. The second-order rate constants (log k(2)) correlated linearly with the electrophilicity parameters E of the electrophiles according to the correlation log k(2) = s(N + E) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957), allowing us to determine the nucleophilicity parameters N and s for the pyridone anions. The reactions of the 2- and 4-pyridone anions with stabilized amino-substituted benzhydrylium ions and Michael acceptors are reversible and yield the thermodynamically more stable N-substituted pyridones exclusively. In contrast, highly reactive benzhydrylium ions (4,4'-dimethylbenzhydrylium ion), which react with diffusion control, give mixtures arising from N- and O-attack with the 2-pyridone anion and only O-substituted products with the 4-pyridone anion. For some reactions, rate and equilibrium constants were determined in DMSO, which showed that the 2-pyridone anion is a 2-4 times stronger nucleophile, but a 100 times stronger Lewis base than the 4-pyridone anion. Quantum chemical calculations at MP2/6-311+G(2d,p) level of theory showed that N-attack is thermodynamically favored over O-attack, but the attack at oxygen is intrinsically favored. Marcus theory was employed to develop a consistent scheme which rationalizes the manifold of regioselectivities previously reported for the reactions of these anions with electrophiles. In particular, Kornblum's rationalization of the silver ion effect, one of the main pillars of the hard and soft acid/base concept of ambident reactivity, has been revised. Ag(+) does not reverse the regioselectivity of the attack at the 2-pyridone anion by increasing the positive charge of the electrophile but by blocking the nitrogen atom of the 2-pyridone anion.