Reactions of Carbocations

Carbocations are strong Lewis acids which occur as intermediates in reactions following the SnI (Chapter 9) or El (Chapter 10) mechanistic routes. The most obvious and 

X = halide - alkyl halides X = H2O — alcohols X = HOR or HOAr — ethers X - RC02H or ArC02H - esters X = NR3 — alkylammonium salts X = RSH — thioethers (thiols if R = H) 

If the nucleophilic site (HOMO) involves a nonbonded pair of electrons (path a), a stable covalently bonded complex will form. If the HOMO is a a bond, direct reaction is unlikely unless the bond is high in energy and sterically exposed, as in a three-membered ring, but if the bond is to H, hydride abstraction may occur (path b, steps 1 and 2) or a hydride bridge may form (path 6, step 1). The last two possibilities are discussed further in Chapter 10. If the HOMO is a n bond, a n complex may result (path c, step 1), or, more commonly, donation of the n electrons results in the formation of a a bond at the end where the n electron density was higher, the other end becoming Lewis acidic in the process (path c, steps 1 and 2). The effects of substituents on olefin reactivity were discussed in Chapter 6. 

Carbocations usually undergo elimination reactions, addition reactions, reactions with nucleophiles and rearrangements. 

A carbocation may react with an alkene to produce another carbocation. 

The alkyl carbocations formed from alkyl halides, aikenes and alcohols act as an electrophile in Friedel-Crafts alkylation reactions.  

The Friedel-Crafts alkylation mechanism involves the generation of an electrophile by adding an alkyl halide to the Lewis acid aluminium trichloride, which results in the formation of an organometallic complex. In this complex the carbon attached to the chlorine has a great deal of positive charge character (in fact, for practical purposes it is considered as a carbocation). 

Molecular rearrangements involving carbocations as reactive intermediates are very common in organic chemistry. The first-formed carbocation, which is less stable, can rearrange by 1,2-shift of either H or alkyl group to more stable carbocation. 

There are three important reactions of carbocations rearrangements, addition of a nucleophile, and elimination, usually of a proton. Since rearrangements involve conversion of one carbocation into another, these reactions will need to be completed to give an uncharged product by addition of a nucleophile or by elimination. 

The primary alcohol 16 reacts with HBr to give the rearranged bromide 19 (reaction 5.16). Protonation will give the oxonium ion 17 as the water molecule leaves in the second step, the methyl group migrates so that the tertiary carbocation 18 is formed, which adds a bromide ion to give the final product. 

The diol 20 (pinacol) rearranges to pinacolone 22 in the presence of acid in the second step the methyl group migrates with its bonding electrons to give the stabilized cation 21, which loses a proton to give the final ketone 22 (reaction 5.17). 

Carbocations, however formed, are very electrophilic. They react readily with nucleophiles, as shown in reaction (5.18). These reactions are important as steps in electrophilic addition to double bonds and unimolecular nucleophilic substitution (SnI) reactions. 

The electrophile adds first to give the more stabfe cation intermediate. 

The earboeations being highly reactive intermediates of very short life react further without being isolated and give stable products. In general they give the following reactions  

In this process the elimination of a proton results in the formation of an alkene. Thus the dehydration of alcohols gives rise to alkene in presence of cone. H2SO4 

So earbocations can adopt two pathways to give the stable product. 

A carbocation may add to an alkene producing a new positive eharge at a new position as shown in the following example. 

Formed by any of the two methods, the new carbocation reacts further to stabilize itself. This generally happens either by reacting with a nucleophile or by the loss of a proton. 

The product of a substitution reaction that follows the limiting Sf 2 mechanism is determined by the identity of the nucleophile. The nucleophile replaces the leaving group and product mixtures are obtained only if there is competition from several nucleophiles. Product mixtures from ionization mechanisms are often more complex. For many carbocations there are two competing processes that lead to other products elimination and rearrangement. We discuss rearrangements in the next section. Here we consider the competition between substitution and elimination under solvolysis conditions. We return to another aspect of this competition in Section 5.10, when base-mediated elimination is considered. 

For both tertiary cations and secondary benzylic carbocation, the ratio of substitution to elimination is quite high. For example, for l-(/i-tolyl)ethyl cation in 50 50 TFE-water, the ratio is 1400. ° For the fert-butyl cation, the ratio is about 30 in water and 60 in 50 50 TFE-water. These ratios are on the order of 10 if account is taken of the need for solvent reorganization in the substitution process. The generalization is that under solvolysis conditions, tert-alkyl and sec-benzyl carbocations prefer substitution to elimination. 

The origin of this preference has been considered by Richard and co-workers. One aspect of the puzzle can be seen by applying Hammond s postulate. Since the competing reactions have early transition states, it is unlikely that the difference in product stability governs the competition. Instead, the substitution process appears to have a smaller intrinsic barrier (in the context of the Marcus equation see Section 3.2.4). The elimination reaction appears to have a barrier that is 3 kcal higher, at least for ec-benzylic systems. The structural basis of this difference has not been established, but it may be related to the fact that the elimination process has a bond-breaking component, whereas substitution requires only bond formation. 

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Formed by either process, carbocations are most often short-lived transient species and react further without being isolated. The intrinsic barriers to formation and reaction of carbocations has been studied. ... 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

The elimination reactions of carbocations (type b) will be discussed in more detail subsequently (p. 248), but the rearrangement reactions (type d) are of sufficient interest and importance to merit further study now. 

The free energies of activation for these two reactions of carbocations are not very different from one another. 

The determinations of absolute rate constants with values up to ks = 1010 s-1 for the reaction of carbocations with water and other nucleophilic solvents using either the direct method of laser flash photolysis1 or the indirect azide ion clock method.8 These values of ks (s ) have been combined with rate constants for carbocation formation in the microscopic reverse direction to give values of KR (m) for the equilibrium addition of water to a wide range of benzylic carbocations.9 13... 

In summary, there now exists a body of data for the reactions of carbocations where the values of kjkp span a range of > 106-fold (Table 1). This requires that variations in the substituents at a cationic center result in a >8 kcal mol-1 differential stabilization of the transition states for nucleophile addition and proton transfer which have not yet been fully rationalized. We discuss in this review the explanations for the large changes in the rate constant ratio for partitioning of carbocations between reaction with Bronsted and Lewis bases that sometimes result from apparently small changes in carbocation structure. 

To what extent are the variations in the rate constant ratio /cs//cpobserved for changing structure of aliphatic and benzylic carbocations the result of changes in the Marcus intrinsic barriers Ap and As for the deprotonation and solvent addition reactions It is not generally known whether there are significant differences in the intrinsic barriers for the nucleophile addition and proton transfer reactions of carbocations. 

Rate constants for the reactions of carbocations with added nucleophiles are obtained in LFP experiments as the slopes of linear plots of first-order rate constants for cation decay against the concentrations of added nucleophile. One of the first detailed studies using LFP showed that rate constants for the parent triphenylmethyl cation did not adhere to the simple Ritchie N+ relation of Eq. 13, but that the slope of a plot of log Nu versus N+ was significantly < 1 This finding has been verified... 

In a series of reports published over the last 10-15 years, Mayr and co-workers obtained second-order rate constants for reactions of carbocations and other electrophiles such as metal-7i complexes with a series of nucleophiles, especially 7t-nucleophiles where a C C bond is formed. An impressive body of reactivity data has been accumulated, and, including data from other groups, correlated by the following equation. 

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. 

Table 2 Yukawa-Tsuno parameters for the reaction of carbocations and nitrenium ions with H20. ...

Finally, two studies have reported on the reactions of carbocations with Mg atoms using mass spectrometry The types of products formed depend on the nature of the carbocation. The labeled methanium ion, CH4D+, reacts via proton transfer (equation 11), deuteron transfer (equation 12) and charge transfer (equation 13). The ethyl cation reacts via charge transfer (equation 14) while the tert-butyl cation reacts via proton transfer (equation 15). In all cases there was no evidence for formation of an organomagnesium species. 

Problem 6.58 List the five kinds of reactions of carbocations and give an example of each, (a) They combine with nucleophiles. 

Intramolecular reactions of carbocations are shown in the following scheme ... 

The typical reactions of carbocation intermediates were discussed in Chapter 7. The solvolysis of alkyl halides is an example of the involvement of carbocations in the SnI mechanism, in other words, where the final outcome is a nucleophilic substitution. The first step is a heterolytic cleavage of the C—X bond. Properties of X which favor heterolytic cleavage, namely electronegativity difference with carbon (the larger, the better) and the degree of overlap of the X orbital with the spn orbital of carbon (the smaller the better), have already been elucidated (Chapter 4). The transition state has partial... 

We summarize here a procedure to predict the feasibility and the stereochemistry of thermally concerted reactions involving cyclic transition states. The 1,2 rearrangement of carbocations will be used to illustrate the approach. This is a very important reaction of carbocations which we have discussed in other chapters. We use it here as an example to illustrate how qualitative MO theory can give insight into how and why reactions occur ... 

Thereafter, a rearrangement occurs resembling the reactions of carbocations (Sections 8-9B and 15-5E). When the cleavage of the N—O bond occurs, the nitrogen atom would be left with only six valence electrons. However, as the bond breaks, a substituent R on the neighboring carbon moves with its bonding... 

The extension of equilibrium measurements to normally reactive carbocations in solution followed two experimental developments. One was the stoichiometric generation of cations by flash photolysis or radiolysis under conditions that their subsequent reactions could be monitored by rapid recording spectroscopic techniques.3,4,18 20 The second was the identification of nucleophiles reacting with carbocations under diffusion control, which could be used as clocks for competing reactions in analogy with similar measurements of the lifetimes of radicals.21,22 The combination of rate constants for reactions of carbocations determined by these methods with rate constants for their formation in the reverse solvolytic (or other) reactions furnished the desired equilibrium constants. 

There have been more equilibrium measurements for reactions of carbocations with azide than halide ions. Regrettably, there is little thermodynamic data on which to base estimates of relative values of pARz and pAR using counterparts of Equations (17) and (18) with N3 replacing Cl. Nevertheless, a number of comparisons in water or TFE-H20 mixtures have been made87,106,226,230 and Ritchie and Virtanen have reported measurements in methanol.195 The measurements recorded below are for TFE-H20 and show that whereas pA" 1 is typically 4 log units more positive than pA R. pA Rz is eight units more negative. The difference should be less in water, perhaps by 2 log units, but it is clear that azide ion has about a 1010-fold greater equilibrium affinity for carbocations than does chloride (or bromide) ion. 

The origin of intrinsic barriers to reactions of carbocations has been discussed by Richard.8 He suggests that reaction of water with a carbocation possessing a strongly localized positive charge such as CH3+ will not only be favorable thermodynamically but possess a very low intrinsic barrier. By contrast, a high intrinsic barrier is associated characteristically with an SN2 reaction, in which... 

In conclusion, it can also be pointed out that in principle a large value of A is itself sufficient to account for an extended linear free energy relationship. However, as Mayr has noted this is only true if the slope of the plot is O.5.238 Moreover, if the Marcus expression offers a quantitative guide to the degree of curvature of a free energy relationship (and it is by no means clear that it does),228 it is evident that the intrinsic barriers to reactions of carbocations with familiar nucleophiles are insufficiently large to account for the lack of curvature. 

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