Carbocations reactivity, mechanisms

The classical treatment for the quantitative determination of the steric effects operative in molecules was developed by Westheimer. Steric effects were considered as the sum of various independent strain producing mechanisms (bond strain, angle strain, torsional strain, non-bonded interaction strain). Westheimer s assumptions proved to be the fundamental basis for the BIGSTRN program as well as for all subsequent molecular mechanics treatments of neutral hydrocarbons and carbocations. Reactivities ranging over 10 ° could be correlated by the strain differences between cation and the neutral precursor. Gleicher and Schleyer s work was a historical breakthrough in the development of molecular mechanics and provided the basis for the predictions of rate constants of solvolysis reactions. For the first time chemical reactions could reliably be predicted by the means of computational chemistry. 

The reactivity order parallels the ease of carbocation formation Increasing rate of elimination by the El mechanism... 

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... 

Both compounds react by an S l mechanism and their relative rates reflect their acti vation energies for carbocation formation Because the allylic chloride is more reactive we reason that it ionizes more rapidly because it forms a more stable carbocation Struc turally the two carbocations differ m that the allylic carbocation has a vinyl substituent on Its positively charged carbon m place of one of the methyl groups of tert butyl cation... 

The rate of addition depends on the concentration of both the butylene and the reagent HZ. The addition requires an acidic reagent and the orientation of the addition is regioselective (Markovnikov). The relative reactivities of the isomers are related to the relative stabiUty of the intermediate carbocation and are isobutylene 1 — butene > 2 — butenes. Addition to the 1-butene is less hindered than to the 2-butenes. For hydrogen bromide addition, the preferred orientation of the addition can be altered from Markovnikov to anti-Markovnikov by the presence of peroxides involving a free-radical mechanism. 

This elimination reaction is the reverse of acid-catalyzed hydration, which was discussed in Section 6.2. Because a carbocation or closely related species is the intermediate, the elimination step would be expected to favor the more substituted alkene as discussed on p. 384. The El mechanism also explains the general trends in relative reactivity. Tertiary alcohols are the most reactive, and reactivity decreases going to secondary and primary alcohols. Also in accord with the El mechanism is the fact that rearranged products are found in cases where a carbocation intermediate would be expected to rearrange ... 

The heats of formation are less suited to characterizing the stability and/or reactivity of carbocations as models of cationic chain ends in cationic polymerizations71). Model reactions closely connected to the cationic polymerization mechanism are better suited to this characterization, for example ... 

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. 

Carboxylic acids are oxidized by lead tetraacetate. Decarboxylation occurs and the product may be an alkene, alkane or acetate ester, or under modified conditions a halide. A free radical mechanism operates and the product composition depends on the fate of the radical intermediate.267 The reaction is catalyzed by cupric salts, which function by oxidizing the intermediate radical to a carbocation (Step 3b in the mechanism). Cu(II) is more reactive than Pb(OAc)4 in this step. 

For over 35 years, the quinone methide species has been invoked as a reactive intermediate in bioreductive alkylation and in other biological processes.8 29 Generally, there is only circumstantial evidence that the quinone methide species forms in solution. Conceivably, the O-protonated quinone methide (i.e., the hydroquinone carbocation) could be the electrophilic species. If so, bioreductive alkylation may simply be an SN1 reaction. Also, there are questions concerning the mechanism of quinone methide... 

Simple tertiary carbocations represent a benchmark against which to compare the reactivity of other a-methyl carbocations. Therefore, it is necessary to deal with complex questions about the mechanism for substitution and elimination reactions at tertiary aliphatic carbon in order to evaluate the rate constant... 

The propensity of S-S dications to undergo dealkylation was found to decrease in the order of methyl > ethyl > benzyl. This order of reactivity parallels the increase in the stability of the corresponding carbocations.94 Dealkylation of dication 77 affords thiosulfonium salt 78 in quantitative yield.95 Kinetic studies suggest SN1 mechanism of dealkylation. In addition, reaction of sulfoxide 79 with a substituent chiral at the a-carbon results in racemic amide 80 after hydrolysis. 

In contrast to this mechanism, the one proposed in our work operates direct from the oxidation state of the alkane feedstock. The same alkyl cation intermediate can lead to both alkane isomerization (an alkyl cation is widely accepted as the reactive intermediate in these reactions) and we have shown in this paper that a mechanistically viable dehydrocyclization route is feasible starting with the identical cation. Furthermore, the relative calculated barrier for each of the above processes is in accord with the experimental finding of Davis, i.e. that isomerization of a pure alkane feedstock, n-octane, with a dual function catalyst (carbocation intermediate) leads to an equilibration with isooctanes at a faster rate than the dehydrocyclization reaction of these octane isomers (8). 

The SnI mechanism requires initial loss of the leaving group to generate a reactive carbocation. 

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