Pinacol rearrangement results

From Table 2 (entry 5) and Table 3 (entry 5) it is apparent that the Ti-Al-Beta catalyzed pinacol rearrangement results in a higher yield of pinacolone 4 than the direct rearrangement starting from the epoxide. Consequently, in order to promote the rearrangement of epoxide 2 to pinacolone 4 via pinacol 3, 2 equivalents of water (relative to the amount of epoxide) were added at the start of the reaction (Scheme 4 conditions A). Furthermore, after formation of the diol a Dean-Stark apparatus was used to remove the excess water (conditions B). 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

The subjects of this section are two reactions that do not actually involve carbo-cation intermediates. They do, however, result in carbon to carbon rearrangements that are structurally similar to the pinacol rearrangement. In both reactions cyclic intermediates are formed, at least under some circumstances. In the Favorskii rearrangement, an a-halo ketone rearranges to a carboxylic acid or ester. In the Ramberg-Backlund reaction, an a-halo sulfone gives an alkene. 

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. 

Treatment of porphyrins with hydrogen peroxide and sulfuric acid, or with osmium tetroxide, results in formation of a dihydroxychlorin (44) under acidic conditions these compounds suffer pinacol rearrangement to give compounds, such as (45), known as gemini-ketones (67TL2185,69JCS(C)564). 

The base-catalysed reaction sequence (formulated in Expt 8.17) is thought to proceed via an intermediate heterocyclic pinacol which on acidification yields the required hydantoin as a result of a pinacolic rearrangement. The procedure is applicable in general to diaryl-1,2-diketones. 

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 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 ... 

Among the most famous examples of a reaction involving a 1,2-alkyl shift is the pinacol rearrangement. This reaction, shown in Scheme 5.10, results in the conversion of a vicinal diol to a ketone. 

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. 

Using our knowledge of alcohol reactions, we can explain results that seem strange at first glance. The following dehydration is an example of the pinacol rearrangement ... 

The formation of /3-silicon-stabilized cations from y-hydroxysilanes results from the normal pattern of pinacol rearrangements, where hydride and phenyl migration is common. Desilylation then also affords an alkene [110]. If the alkyl group is a ring residue, only hydride migration is observed (Eq. 64). 

The second example looks at first to be a similar pinacol rearrangement. But the resulting ketone cannot easily be transformed into the product. 

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. 

All classes of vicinal diols (primary, secondary, tertiary, alkyl- or aryl-substituted) will undergo the pinacol rearrangement, and many acids and solvents have been used for this purpose. Various procedural modifications have been introduced over the years for particular glycols, but sulfuric acid remains the most commonly employed catalyst. The use of 25% H2SO4, as recommended in the procedure of Adams, affords pinacolone in essentially quantitative yield. In some instances better results are obtained when cold concentrated acid is used as the solvent. The choice of reagents and conditions is important, and can completely alter the course of the reaction. For example, pinacol also serves as the starting material for the synthesis of 2,3-dimethylbutadiene, formed by slow distillation of a mixture of the diol and catalytic HBr. ... 

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. 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

The stereochemistry of 6,2-H shifts is endo, endo. Treatment of acid (760) with 50% sulfuric acid results in formation of lactone (761), contaminated by less than 3% of the 2-H species which would arise by 6,2 shift of exo-D531V The pinacolic rearrangement of labeled diol (744a) produces ketone (747a) by way of an endo, endo 6,2-D shift532). 

The isomerization of endo-trimethylenenorbomane to the exo isomer is efficiently catalyzed by superacid systems in cyclohexane or Freon-113 (1,1,2-tri-chloro-l,2,2-trifluoroefhane) [65]. The fd (SO,l l-Sbl -, system is also effective for isomerization of trimefhylenenorbornane to adamantane, although a stoichiometric amount of the acid is necessary to obtain good results [66]. SbCl and SbClj-AgSbFg promote the pinacol rearrangement of 1,2-diols and their trimethylsilyl ethers (Scheme 14.27) [67]. 

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