Pinacol rearrangement carbocation intermediates

While the hydride shift illustrated in Scheme 5.12 cannot occur as a part of the pinacol rearrangement, the intermediate carbocation is subject to alkyl migrations. As shown in Scheme 5.13, a 1,2-alkyl shift results in transfer of the cation from a tertiary center to a center adjacent to a heteroatom. As the oxygen heteroatom possesses lone electron pairs, these lone pairs serve to stabilize the cation. Thus, the illustrated 1,2-alkyl shift transforms a carbocation into a more stable carbocation. 

The pinacol rearrangement is a dehydration reaction that converts a 1,2-diol into a ketone. The reaction involves two carbocation intermediates. 

Isomerization of substituted styrene oxides allows the synthesis of aldehydes in high yields726 [Eq. (5.275)]. Cycloalkene oxides do not react under these conditions, whereas 2,2,3-trimethyloxirane gives isopropyl methyl ketone (85% yield). Isomerization of oxiranes to carbonyl compounds is mechanistically similar to the pinacol rearrangement involving either the formation of an intermediate carbocation or a concerted mechanism may also be operative. Glycidic esters are transformed to a-hydroxy-/3,y-unsaturated esters in the presence of Nafion-H727 [Eq. (5.276)]. 

Although these types of bridged phenonium ions are accepted intermediates in a number of reactions, they do not appear to be involved in the pinacol rearrangement (see Schubert, W. M. LeFevre, P. H. J. Am. Chem. Soc. 1972, 94, 1639). Stabilization of the carbocation 4-10 by resonance with the ojgrgen substituent may be a factor in determining the preference for phenyl migration over phenonium ion formation in the pinacol rearrangement. 

The first step of the process is the protonation of one of the hydroxyl groups, which results in the loss of a water molecule to give a carbocation intermediate. This intermediate undergoes a /"f,27-shift to give a more stable carbocation that upon the loss of proton gives the product. The pinacol rearrangement was shown to be exclusively intramolecular, and both inversion and retention were observed at the migrating center. 

The evidence for carbocation intermediates in the pinacol rearrangement is compelling for some substrates and conditions. Bunton" found that pinacol itself that was recovered from O-enriched aqueous sulfuric acid had incorporated an appreciable amount of solvent oxygen. Under these conditions the reaction goes to completion, i.e. the incorporation cannot be due to reversible formation of diol from pina-... 

The pinacol rearrangement represents another example of loss of -OH under acidic conditions with concomitant migration. One could draw a mechanism with an intermediate carbocation, but this carbocation would be destabilized by the inductive effect of the neighboring OH group. 

The reaction was first described for pinacol (2,3-dimethyl-2,3-butanediol), a ditertiary 1,2-diol and catalyzed by sulfuric acid (73). Now it is known that the pinacol rearrangement is characteristic of all types of 1,2-diols, and most electrophilic catalysts are capable of promoting the process. Two possible mechanisms may account for the experimental observations. The stepwise mechanism involves the )8-hydroxy carbocationic intermediate 6 and the pentacoordinate carbocation 7 (Scheme 1). According to the concerted mechanism, the product carbonyl compoimd is formed through the hypercoordinate intermediate 8. 

The stability of the intermediate carbocations affects the rate-determining step in the pinacol rearrangement (76). The loss of water, that is the formation of the first carbocation, is rate determining when this has a low stability. When a highly stable cation, in contrast, is formed, the migration of the substituent becomes rate determining. 

Due to the symmetry of the carbocation intermediate, pinacol rearrangements of acyclic substrates are rarely stereoselective. However, conformational constraints in cyclic systems can lead to high stereoselectivities. The reactivity of the set of conformationally-locked stereoisomers 9-12 when treated with a Lewis acid is illustrative. Regardless of the stereochemistry at C-1, both C-2 (5) diastereomers (9 and 10) yield only the ketone a-(S) stereoisomer, indicating hydride migration proceeds stereoselectively from the bottom face of the ring system (pathway... 

The carbocation intermediate in a pinacol rearrangement could be stabilized by intramolecular electron donation from the adjacent hydroxyl group to form a protonated epoxide. Indeed, epoxides have, on occasion, been isolated under pinacol rearrangement conditions and have been implicated as intermediates as well. For example, when (-)-benzoin was treated with methylmagnesium iodide followed by dilute aeid, an optically-active epoxide was isolated. " Further treatment of the epoxide with acid generated a racemic ketone. 

Pinacol Rearrangement (Section 10.7) Dehydration of a glycol involves formation of a carbocation intermediate, rearrangement, and loss of H+ to give an aldehyde or a ketone. 

Rearrangements may also proceed via intermediates that are essentially cations, anions, or radicals, though those involving carbocations, or other electron-deficient species, are by far the most common. They may involve a major rearrangement of the carbon skeleton of a compound, as during the conversion of 2,3-dimethylbutan-2,3-diol (pinacol, 42) into 2,2-dimethylbutan-3-one (pinacolone, 43, cf. p. 113) ... 

A methyl group moves from one carbon atom to an adjacent one in order to stabilize an intermediate carbocation. The reaction, also caRed the pinacol-pinacolone rearrangement, j es its name to a class of similar rearrangements. 

In another cascade sequence Kisrch and coworkers utilized substrate 55 as a common intermediate to produce two different carbocycles, relying either on the subsequent pinacol or a [3-1-3] rearrangement of two different, depending on the conditions, carbocations (Scheme 7.29). 

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