The Reactivity-Selectivity Principle

Radical additions lo double bonds are, in general, highly exothermic processes and rates increase with increasing temperature. The rcgiospccificity of addition to double bonds and the relative reactivity of various olefins towards radicals are also temperature dependent. Typically, specificity decreases with increasing temperature (the Reactivity-Selectivity Principle applies). However, a number of exceptions to this general rule have been reported. 8 63... 

This Lewis acid ability of increasing both the reaction rate and the selectivity of the cycloaddition is surprising, since in other catalyzed reactions an increase in the reaction rate is accompanied by a decreased selectivity according to the reactivity selectivity principle. This apparently contradictory behavior of the Lewis acids has been explained theoretically [6,7]. 

In other words, under these restrictive conditions, outer sphere electron-transfer reactions obeying the Marcus-Hush model are typical examples where the Hammond-Leffler postulate and the reactivity-selectivity principle (see, for example, Pross, 1977, and references cited therein, for the definition of these notions) are expected to apply. 

In this instance, not only do the calculations bring into question the validity (or at least the generality) of the reactivity-selectivity principle but, more importantly, they open up a route to actually improving reaction selectivity. Note, in particular, the close parallels between the way this investigation was carried out and the way in which an experimental study would be performed. 

The roles of carbocations in commercially important hydrocarbon transformations are still not perfectly understood. The same can be said for carbocations in biological systems. Significant questions concerning reactivity still need to be explained. Why do so many reactions of carbocations show constant selectivity, in violation of the reactivity-selectivity principle Is it possible to develop a unified scale of elec-trophilicity-nucleophilicity, in particular one that incorporates these parameters into the general framework of Lewis acidity and basicity. Finally, quite sophisticated synthetic transformations are being developed that employ carbocations, based upon insights revealed by the mechanistic studies. 

Reactivity of X. The more reactive Cl- is less selective and more influenced by the probability factor. The less reactive Br- is more selective and less influenced by the probability factor. As summarized by the reactivity-selectivity principle If the attacking species is more reactive, it will be less selective, and the yields will be closer to those expected from the probability factor. 

According to the reactivity-selectivity principle, reduced reactivity of a compound is expected to be accompanied by increased selectivity of its reactions. Exactly this was observed in early experiments by Steele and Weber37 when the insertion reaction of dimethylsilylene (13) into the O-H bond of alcohols was performed in different solvents In a more polar solvent such as THF the reaction of the silylene with the... 

Mechanisms, of proton transfer between oxygen and nitrogen acids and bases in aqueous solutions, 22, 113 Mechanisms, organic reaction, isotopes and, 2, 1 Mechanisms of reaction, in solution, entropies of activation and, 1, 1 Mechanisms of reaction, of /3-lactam antibiotics, 23, 165 Mechanisms of solvolytic reactions, medium effects on the rates and, 14, 10 Mechanistic analysis, perspectives in modern voltammeter basic concepts and, 32, 1 Mechanistic applications of the reactivity-selectivity principle, 14, 69 Mechanistic studies, heat capacities of activation and their use, 5, 121 Mechanistic studies on enzyme-catalyzed phosphoryl transfer, 40, 49 Medium effects on the rates and mechanisms of solvolytic reactions, 14, 1 Meisenheimer complexes, 7, 211... 

An extensive review with many examples125 shows that the reactivity-selectivity principle cannot be used to predict the selectivity of a reaction except in unique systems where one reaction is close to or diffusion controlled. The relative importance of the Hammond effect and the frontier-orbital effects determines the reactivity-selectivity relationship that will be found in a particular system. The review also concludes that the Hammond-Leffler a-value cannot be used as an indicator of transition-state structure. 

Selectivity versus Reactivity. The "reactivity-selectivity principle" (RSP) states that "in a set of similar reactions, the less reactive the reagent, the more selective it is in its attack" (451. This principle is widely held, but its generality has recently been questioned (28.46-481. The reactivity data assembled in Tables IV through VIII appear to provide an opportunity to examine the validity of the RSP, using log(kA/ka)sN as a measure of the selectivity of a haloaliphatic compound between nucleophiles A and B. 

Kinetic studies at 100 °C revealed that ethyl /V-ethylthionocarbamate, EtOC(S)NHEt, was hydrolysed in acid by an Al mechanism and in base by a BAc2 mechanism.53 The concerted mechanism proposed for the aminolysis at 30 °C in MeCN of aryl /V-ethyl thionocarbamates, (XC6H40)C(S)NHEt, by benzylamine was supported by a negative cross-interaction constant, pxz = —0.87 and failure of the reactivity-selectivity principle.54 Similar conclusions, for the same reasons, were made for the aminolysis of the corresponding thiolocarbamates, (XC6H4S)C(0)NIIFL, by benzylamine in MeCN at 10 °C.55... 

The reactivity-selectivity principle seems to be intuitively sound. But data indicate otherwise. The work of Mayr and others has shown that there are many reactions in which selectivity is not compromised at the expense of reactivity. Rates increase, but relative reactivities, that is, selectivities, remain constant. The example discussed above is an exception and conceptually very tempting. It teaches us the lesson that our models about chemistry must be continually questioned and refined. 

The reactivity-selectivity principle holds when one of the reference reactions being considered occurs close to the diffusion-controlled limit. At or near this limit, reactions are very fast and not selective. Below this point, selectivity reveals itself. Compare two analogous reactions that differ substantially in rate, neither of which occurs near the diffusion-controlled limit and each will exhibit similar selectivities, though the rate by which these reactions occur will differ. 

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