Carbocation pinacol rearrangement

The pinacol rearrangement is frequently observed when geminal diols react with acid. The stmcture of the products from unsymmetrical diols can be predicted on the basis of ease of carbocation formation. For example, l,l-diphenyl-2-metltyl-l,2-propanediol rearranges to... 

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

The diazotization reaction generates the same type of /i-hydroxy carbocation that is involved in the pinacol rearrangement. (See Section 5.6 in Part A for a discussion of the formation of carbocations from diazo compounds.)... 

Pinacol rearrangement is a dehydration of a 1,2-diol to form a ketone. 2,3-drmethyl-2,3-butanediol has the common name pinacol (a symmetrical diol). When it is treated with strong acid, e.g. H2SO4, it gives 3,3-dimethyl-2-butanone (methyl r-butyl ketone), also commonly known as pinacolone. The product results from the loss of water and molecular rearrangement. In the rearrangement of pinacol equivalent carbocations are formed no matter which hydroxyl group is protonated and leaves. 

In order to answer the question about inherent migratory aptitudes, the obvious type of substrate to use (in the pinacol rearrangement) is RR C—CRR , since the same carbocation... 

J. F. Duncan and K. R. Lynn, J. Chem. Soc., 3512, 3519 (1956) J. B. Ley and C. A. Vernon, Chem. Ini. (London), 146 (1956).] That the rate-determining step can be the migration when the first-formed carbocation is particularly stable has been shown by Schubert and LeFevre [note 18(b)]. These workers subjected 1,1-diphenyl-2-methyl- 1,2-propanediol to the pinacol rearrangement and found that deuterium substitution in the migrating methyls caused the reaction to slow down. 

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)]. 

The pinacol rearrangement is a dehydration of an alcohol that results in an unexpected product. When hot sulfuric acid is added to an alcohol, the expected product of dehydration is an alkene. However, if the alcohol is a vicinal diol, the product will be a ketone or aldehyde. The reaction follows the mechanism shown, below. The first hydroxyl group is protonated and removed by the acid to form a carboca-tion in an expected dehydration step. Now, a methyl group may move to fonn an even more stable carbocation. This new carbocation exhibits resonance as shown. Resonance Structure 2 is favored because all tire atoms have an octet of electrons. The water deprotonates Resonance Structure 2, forming pinacolone and regenerating the acid catalyst. 

The proposed mechanism for the reaction is shown in Scheme 13.75. In the first step, the oxonium cation 208, formed by TfOH-catalyzed condensation of an aldehyde with alcohol 206, undergoes an intramolecular cyclization to form the tertiary carbocation 209. In a subsequent step, cation 209 undergoes a pinacol rearrangement, leading to the observed tetrahydropyran 205. 

The most general method for the synthesis of tetrahydrofurans based upon the IMSC methodology was developed by Overman et al. [53, 54, 94—96] For example, condensation of alcohol 221 with an aldehyde or a ketone in the presence of a Lewis acid leads to the formation of the carbocations 222a,b. The tertiary carboca-tion 222a undergoes a pinacol rearrangement and forms the desired heterocycle 224 (Scheme 13.82). Overman et al. used this approach during the synthesis of the various cladiellin diterpenes, which possess the core skeleton 224 [53]. 

The pinacol rearrangement is a useful reaction that proceeds via a carbocation rearrangement. Treatment of 2,3-dimethyl-2,3-butanediol, also known as pinacol, with acid results in the formation of a ketone, pinacolone ... 

The mechanism for this reaction, shown in Figure 22.5, involves a carbocation rearrangement that occurs by an allowed [1,2] sigmatropic shift. The product of this rearrangement, a protonated ketone, is considerably more stable than the initial carbocation, so the migration is quite favorable. Another example of the pinacol rearrangement is provided in the following equation ... 

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 reaction they needed for the last stage is a pinacol rearrangement—the primary hydroxyl group needs persuading to leave as the ring expands. The problem is, of course, that the tertiary hydroxyl group is much more likely to leave since it leaves behind a more stable carbocation. 

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-... 

Other unsymmetrical diols, prepared (inefficiently) by the coupling of mixtures of ketones, have been studied. The preferred cation argument is also found to be applicable to mixed medium-ring analogs, i.e. the kinetically favored pinacol rearrangement product is that predicted by consideration of the relative stabilities of the two possible, initially formed, carbocations. ° Earlier work with these compounds may have given misleading results due to product instability. To illustrate, Mundy observed that (24) is converted to (25) as the temperature is increased. 

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. 

---