Rate-determining step electrophilic additions

Both steps m this general mechanism are based on precedent It is called elec trophilic addition because the reaction is triggered by the attack of an acid acting as an electrophile on the rr electrons of the double bond Using the two rr electrons to form a bond to an electrophile generates a carbocation as a reactive intermediate normally this IS the rate determining step... 

Systematic studies of the selectivity of electrophilic bromine addition to ethylenic bonds are almost inexistent whereas the selectivity of electrophilic bromination of aromatic compounds has been extensively investigated (ref. 1). This surprising difference arises probably from particular features of their reaction mechanisms. Aromatic substitution exhibits only regioselectivity, which is determined by the bromine attack itself, i.e. the selectivity- and rate-determining steps are identical. 

With regard to the composition of the electrical effect, examination of the p values reported in Table XVII shows that in six of the sets which gave significant correlation, the localized effect is predominant (in these sets, either Pr < 50 or / is not significant). Thus it would appear that in so far as substituent effects are concerned, there are two major classes of electrophilic addition to the carbon-carbon double bond predominance of the localized effect or predominance of the delocalized effect. This behavior may well be accounted for in terms of the reaction mechanism. The rate-determining step in the electrophilic addition reaction is believed to be the formation of an intermediate which may be either bridged or a free carbonium ion. 

The rate-determining step in this process is the oxidative addition of methyl iodide to 1. Within the operating window of the process the reaction rate is independent of the carbon monoxide pressure and independent of the concentration of methanol. The methyl species 2 formed in reaction (2) cannot be observed under the reaction conditions. The methyl iodide intermediate enables the formation of a methyl rhodium complex methanol is not sufficiently electrophilic to carry out this reaction. As for other nucleophiles, the reaction is much slower with methyl bromide or methyl chloride as the catalyst component. 

In addition to simple electron transfers in which no chemical bond is either broken or formed, numerous organic reactions, previously formulated by movements of electron pairs, are now understood as processes in which an initial electron transfer from a nucleophile (reductant) to an electrophile (oxidant) produces a radical ion pair, which leads to the final products via the follow-up steps involving cleavage and formation of chemical bonds [11-23], The follow-up steps are usually sufficiendy rapid to render the initial electron transfer the rate-determining step in an overall irreversible transformation [24], In such a case, the overall reactivity is determined by the initial electron-transfer step, which can also be well designed based on the redox potentials and the reorganization energies of a nucleophile (reductant) and an electrophile (oxidant). 

Kinetic isotope effect measurements support this interpretation. A small kinetic isotope effect (kR/kD = 0.71) is observed for p-methoxyphenol in agreement with a ratedetermining nucleophilic attack, while a large kinetic isotope effect (kR/kR = 5.27), observed for p-trifluoromethylphenol, strongly supports a mechanism in which a phenolic H (or D) is transferred to 39 in the rate-determining step. Unfortunately, 39 is a symmetric disilene so that diastereoselectivity could not be determined. It will be interesting to examine whether the diastereoselectivity will be effected by the change in the addition mechanism from electrophilic to nucleophilic. 

Whilst the elementary steps of the reaction were postulated in the earliest publications [3], and remain (globally) even today as the core of the mechanistic discussion, the fine details of the reaction - and in particular those controlling the asymmetric induction - have been highlighted only recently. The first critical mechanism [15a, 45, 46], which is based on pressure-dependence data, established a reversible Michael addition of the nucleophilic base to the activated al-kene (Scheme 5.3). In the following step, the formed zwitterionic enolate 11 adds to the electrophile and forms a second zwitterionic adduct 13. This step was considered to be the rate-determining step (RDS) of the reaction. Subsequent proton transfer and release of the catalyst provides finally the desired product 14. 

To understand this difference in reactivity of various acid derivatives look at the first step in the nucleophilic substitution mechanism (involving the addition of a nucleophile to the electrophilic carbonyl carbon) which is the rate-determining step. Therefore, the more electrophilic this carbon is, the more reactive it will be. The nature of Y has a significant effect in this respect ... 

In contrast, reaction of electron acceptor-substituted phenols exhibits p = +1.72, indicating the development of negative charge at the phenolic oxygen in the rate-determining step for reaction of relatively acidic, weakly nucleophilic phenols with 110, and the addition of 112f exhibits a large primary deuterium kinetic isotope effect of k /kv = 5.3. This is consistent with the electrophilic addition mechanism of equation 85, in which full or partial protonation at silicon precedes nucleophilic attack. 

Although these additions to CO double bonds have some superficial similarities to the electrophilic additions to CC double bonds that were presented in Chapter 11, there are many differences. The acidic conditions mechanism here resembles the mechanism for addition to carbon-carbon double bonds in that the electrophile (the proton) adds first, followed by addition of the nucleophile. However, in this case the first step is fast because it is a proton transfer involving oxygen, a simple acid-base reaction. The second step, the attack of the nucleophile, is the rate-determining step. (Recall that it is the first step, the addition of the electrophile, that is slow in the additions to CC double bonds.) Furthermore, in the case of additions to simple alkenes there is no mechanism comparable to the one that operates here under basic conditions, in which the nucleophile adds first. Because the nucleophile adds in the slow step, the reactions presented in this chapter are termed nucleophilic additions, even if the protonation occurs first. In... 

Because of the presence of nitrogen in the aromatic ring, electrons in pyridine are distributed in such a way that their density is higher in positions 3 and 5 (the P-positions). In these positions, electrophilic substitutions such as halogenation, nitration, and sulfonation take place. On the contrary, positions 2, 4, and 6 (a- and y-positions, respectively) have lower electron density and are therefore centers for nucleophilic displacements such as hydrolysis or Chichibabin reaction. In the case of 3,5-dichlorotrifluoropyridine, hydroxide anion of potassium hydroxide attacks the a- and y-positions because, in addition to the effect of the pyridine nitrogen, fluorine atoms in these position facilitate nucleophilic reaction by decreasing the electron density at the carbon atoms to which they are bonded. In a rate-determining step, hydroxyl becomes attached to the carbon atoms linked to fluorine and converts the aromatic compound into a nonaromatic Meisenheimer complex (see Surprise 67). To restore the aromaticity, fluoride ion is ejected in a fast step, and hydroxy pyridines I and J are obtained as the products [58],... 

Methyl groups at the position of electrophilic attack exert exactly the same enthalpic and entropic effects as in the alkene series (Table 4), and one can summarize that the attack of carbocations at alkenes and at allylsi-lanes, allylgermanes, and allylstannanes follows the same mechanism. The differences between these classes of nucleophiles are encountered after the rate-determining step While ordinary carbocations (produced from alkenes) usually accept a chloride ion to give addition products, the /3-metal-substituted carbocations are generally demetalated to yield the Se2 products. It has been reported, however, that j8-silyl-substituted carbe-nium ions with bulky substituents at silicon may also act as chloride acceptors with the consequence that in these cases allylsilanes yield addition products in the same way as ordinary alkenes do [159],... 

Like the electrophilic addition of HX to an alkene, the addition of HBr to a conjugated diene forms the more stable carbocation in Step [1], the rate-determining step. In this case, however, the carbocation is both 2° and allylic, and thus two Lewis structures can be drawn for it. In the second step, nucleophilic attack of Br can then occur at two different electrophilic sites, forming two different products. 

To understand why some substituents make a benzene ring react faster than benzene itself (activators), whereas others make it react slower (deactivators), we must evaluate the rate-determining step (the first step) of the mechanism. Recall from Section 18.2 that the first step in electrophilic aromatic substitution is the addition of an electrophile (E ) to form a resonance-stabilized carbo-cation. The Hammond postulate (Section 7.15) makes it pos.sible to predict the relative rate of the reaction by looking at the stability of the carbocation intermediate. 

The rate-determining step in the ionic hydrogenation reaction of carbon-carbon double bonds involves protonation of the C==C to form a carbocation intermediate, followed by the rapid abstraction of hydride from the hydride source (equation 45). ° There is a very sensitive balance between several factors in order for this reaction to be successful. The proton source must be sufficiently acidic to protonate the C—C to form the intermediate carbocation, yet not so acidic or electrophilic as to react with the hydride source to produce hydrogen. In addition, the carbocation must be sufficiently electrophilic to abstract the hydride from the hydride source, yet not react with any other nucleophile source present, i.e. the conjugate anion of the proton source. This balance is accomplished by the use of trifluoroacetic acid as the proton source, and an alkylsilane as the hydride source. The alkene must be capable of undergoing protonation by trifluoroacetic acid, which effectively limits the reaction to those alkenes capable of forming a tertiary or aryl-substituted carbocation. This essentially limits the application of this reaction to the reduction of tri- and tetra-substituted alkenes, and aryl-substituted alkenes. 

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