Nucleophilic capture of carbocations

Many radical cations derived from cyclopropane (or cyclobutane) systems undergo bond formation with nucleophiles, typically neutralizing the positive charge and generating addition products via free-radical intermediates [140, 147). In one sense, these reactions are akin to the well known nucleophilic capture of carbocations, which is the second step of nucleophilic substitution via an Sn 1 mechanism. The capture of cyclopropane radical cations has the special feature that an sp -hybridized carbon center serves as an (intramolecular) leaving group, which changes the reaction, in essence, to a second-order substitution. Whereas the SnI reaction involves two electrons and an empty p-orbital and the Sn2 reaction occurs with redistribution of four electrons, the related radical cation reaction involves three electrons. 

Partial but not complete loss of optical activity m S l reactions probably results from the carbocation not being completely free when it is attacked by the nucleophile Ionization of the alkyl halide gives a carbocation-hahde ion pair as depicted m Figure 8 8 The halide ion shields one side of the carbocation and the nucleophile captures the carbocation faster from the opposite side More product of inverted configuration is formed than product of retained configuration In spite of the observation that the products of S l reactions are only partially racemic the fact that these reactions are not stereospecific is more consistent with a carbocation intermediate than a concerted bimolecular mechanism... 

When formulating a mechanism for the reaction of alkynes with hydrogen halides we could propose a process analogous to that of electrophilic addition to alkenes m which the first step is formation of a carbocation and is rate determining The second step according to such a mechanism would be nucleophilic capture of the carbocation by a halide ion... 

The extent to which rearrangement occurs depends on the structure of the cation and foe nature of the reaction medium. Capture of carbocations by nucleophiles is a process with a very low activation energy, so that only very fast rearrangements can occur in the presence of nucleophiles. Neopentyl systems, for example, often react to give r-pentyl products. This is very likely to occur under solvolytic conditions but can be avoided by adjusting reaction conditions to favor direct substitution, for example, by use of an aptotic dipolar solvent to enhance the reactivity of the nucleophile. In contrast, in nonnucleophilic media, in which fhe carbocations have a longer lifetime, several successive rearrangement steps may occur. This accounts for the fact that the most stable possible ion is usually the one observed in superacid systems. 

Polyene Cyclization. Perhaps the most synthetically useful of the carbo-cation alkylation reactions is the cyclization of polyenes having two or more double bonds positioned in such a way that successive bond-forming steps can occur. This process, called polyene cyclization, has proven to be an effective way of making polycyclic compounds containing six-membered and, in some cases, five-membered rings. The reaction proceeds through an electrophilic attack and requires that the double bonds that participate in the cyclization be properly positioned. For example, compound 1 is converted quantitatively to 2 on treatment with formic acid. The reaction is initiated by protonation and ionization of the allylic alcohol and is terminated by nucleophilic capture of the cyclized secondary carbocation. 

The table shows the effect on product ratio of ultrasonic irradiation (Kerry Pulsatron cleaning bath 35 kHz 50 W) during electrolysis. Here there is only 8% of the bicyclohexyl dimeric one-electron product, with approximately 41 % of the two-electron product from nucleophilic capture of the intermediate carbocation. The preponderance of cyclohexene (32 %) over cyclohexane (> 3 %) shows its formation is by proton loss from the carbocation intermediate, since free-radical routes to cyclohexene (i. e. hydrogen atom abstraction) also produce cyclohexane in equal if not greater amounts... 

No comparable micellar effects have been observed in 1,2-alkyl shifts which proceed with inversion of configuration above and below the cmc195 A slight increase in racemization above the cmc may be attributed to delayed nucleophilic capture of the carbocations in the less aqueous micellar environment. 

Nucleophilic capture of the carbocation intermediate by an alcohol molecule leads to an acetal ... 

Nucleophilic capture of the spirooctadienyl cation opens the 3-member ring. This behavior characterizes many reactions of many other cyclopropane-containing carbocations, as well, y-radiolysis of perdeuterated propane forms CsD ions, most of which either transfer D or form isopropyl adducts. As the propane pressure is raised from 1000 mbar to 2000 mbar, however, the isopropyl/ -propyl adduct ratio falls from 30 1 to about 5.5 1. This implies the formation of corner-protonated cyclopropane, which reacts with nucleophiles as though it were an -propyl cation. With increased pressure, vibrationally excited protonated cyclopropane experiences more frequent nonreactive collisions, which deactivate it and slow down its rate of unimolecular isomerization to isopropyl cation. 

In cases where rearrangements are possible, HX additions produce a mixture of products, including those resulting from a carbocation rearrangement as well as those formed without rearrangement (i.e., if the nucleophile captures the carbocation before rearrangement has a chance to occur) ... 

FIGURE 22 5 The diazo mum ion generated by treatment of a primary al kylamine with nitrous acid loses nitrogen to give a car bocation The isolated prod ucts are derived from the carbocation and include in this example alkenes (by loss of a proton) and an al cohol (nucleophilic capture by water)... 

It is not difficult to incorporate this result into the general mechanism for hydrogen halide additions. These products are formed as the result of solvent competing with halide ion as the nucleophilic component in the addition. Solvent addition can occur via a concerted mechanism or by capture of a carbocation intermediate. Addition of a halide salt increases the likelihood of capture of a carbocation intermediate by halide ion. The effect of added halide salt can be detected kinetically. For example, the presence of tetramethylammonium... 

As the intermediate formed in a polyene cyclization is a carbocation, the isolated product is often found to be a mixture of closely related compounds resulting from competing modes of reaction. The products result from capture of the carbocation by solvent or other nucleophile or by deprotonation to form an alkene. Polyene cyclizations can be carried out on reactants that have structural features that facilitate transformation of the carbocation to a stable product. Allylic silanes, for example, are stabilized by desilylation.12... 

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