Rearrangement of carbocations

A reaction that follows this pattern is the acid-catalyzed conversion of diols to ketones, which is known as the pinacol rearrangement. The classic example of this 

Another method for carrying out the same net rearrangement involves synthesis of a glycol monosulfonate ester. These compounds rearrange under the influence of base. 

Ring Expansion of Cyclic Ketones with Diazo Compounds 

There is kinetic evidence that the migration step in these base-catalyzed rearrangements is concerted with ionization. Thus, in cyclopentane derivatives, the rate of reaction depends on the nature of the trans substituent 

This implies that the migration is part of the rate-determining step. 

Although many overall rearrangements can be formulated as a series of 1,2-shifls, both isotopic tracer studies and computational work have demonstrated the involvement of other species. These are bridged ions in which hydride or alkyl groups are partially bound to two other carbons. Such structures can be transition states for hydride and alkyl-group shifts, but some evidence indicates that these structures can also be intermediates. 

The alkyl-bridged structures can also be described as comer-protonated cyclopropanes, since if the bridging C—C bonds are considered to be fiiUy formed, there is an extra proton on the bridging carbon. In another possible type of sfructure, called edge-protonated cyclopropanes, the carbon-carbon bonds are depicted as fiilly formed, with the extra proton associated with one of the bent bonds. MO calculations, sfructural studies under stable-ion conditions, and product and mechanistic studies of reactions in solution have all been apphed to understanding the nature of the intermediates involved in carbocation rearrangements. 

The energy surface for C3H7+ has been calculated at the 6-311G /MP4 level. The 1-and 2-propyl cations and comer- and edge-protonated cyclopropane stractures were 

The 2-butyl cation can be observed under stable-ion conditions. The NMR spectrum corresponds to a symmetrical species, which implies either very rapid hydride shift or a symmetrical H-bridged structure. 

A maximum barrier of 2.5 kcal/mol can be assigned from the NMR data. There have been two extensive MO calculations of the C4H9+ species. At the 6-311G /MP4 level of theory, the H-bridged structure was the most stable found and was about 2 kcal/mol more 

A natural bond orbital analysis of 2-norbomyl and other nonclassical carbocations found evidence for a three-atom, two-center orbital and distribution of charge over all three atoms in the structures. Alkorta, I. Abboud, J. L. M. Quintanilla, E. Davalos, J. Z. /. Phys. Org. Chem. 2003,26, 546. 

For a discussion, see Shubin, V. G. Borodkin, G. I. in Prakash, G. K. S. Schleyer, P. v. R., Eds. Stable Carbocation Chemistry John Wiley Sons New York, 1997, chapter 7. 

Equilibration of protons due to rapid rearrangement in cyclopentyl carbocation (68). 

Apparently a rearrangement takes place rapidly on the NMR time scale, making all nine protons in the molecule equivalent.  

A study of the line broadening of the NMR spectrum of 68 by Saunders revealed an isomerization rate constant of 3.1 x 10 s at —139°C, with a AG of 3.1 kcal/mol. The ESCA analysis of 68, however, suggested the presence in the ion of four uncharged carbon atoms and one positively charged carbon atom. The NMR and ESCA results are different because NMR is a slow camera that sees only an average of the environments a nucleus experiences during its ca. second shutter speed. On the other hand, ESCA is a fast camera with a shutter speed of 10 second, so it is able to detect the discrete cyclopentyl ions.  

The barrier to the hydride and methyl shifts that interconvert the methyl groups in the t-pentyl cation is 10-15 kcal/mol. This shift Involves the formation of secondary ions as transient intermediates.  

The preferred alignment of orbitals for a 1 2-hjrdride or 1 2-alkyl shift invob coplanarlty of the p orbital at the carbonium ion center and the a orbital of the migrating group. 

The extent to which rearrangement occurs depends on the structure of the cation and the nature of the reaction medium. Capture of carbocations by nucleophiles is a process with a very low activation energy, so that only very rapid rearrangements can occur in the presence of nucleophiles. In contrast, in non-nucleophilic media, in which the carbocations have a longer lifetime, many rearrangement steps may occur. This accounts for the fact that the most stable possible ion is usually the one observed in superacid systems. 

The occurrence and extent of rearrangement of carbocations can be studied effectively by isotopic labeling. One case which has been studied in this way is the 2-butyl cation. When 2-butyl tosylate is solvolyzed in acetic acid, only 9% rearrangement occurs in the 2-butyl acetate that is isolated. Thus, under these conditions most of the reaction proceeds by direct participation of the solvent. 

When 2-butyl tosylate is solvolyzed in the less nucleophilic trifluoroacetic acid, a different result emerges. The extent of migration approaches the 50% that would result from equilibration of the two possible secondary cations.  

Two regioisomeric alkenes possible Two stereoisomeric alkenes possible OH 

In the absence of special electronic effects, alkyl groups show a clear dependence on the size of the migrating group. In general, smaller groups migrate before larger 

It is difficult to give an absolute scale for migratory aptitude, however, since migratory aptitude is inevitably linked to the stability of the cation being formed. 

We might expect that the isopropyl cation would be immune to the 1,2 hydride shift exhibited by the cyclopentyl cation, since a simple hydride shift would convert 

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Analogous processes involving cyclizations and rearrangements of carbocations derived from farnesyl pyrophosphate produce a rich variety of structural types m the... 

Substituted dibenzo[6,/]thiepins can be generated from thioxanthene derivatives by the rearrangement of carbocation 1. Compared with other possible cations, the tropylium ion type 1C is favored because of its resonance energy. Depending on the reaction conditions, the thiepin cation can react to give thiepins by loss of a proton, or by trapping a nucleophile, followed by elimination. 

This is less common than rearrangement of carbocations, but it does occur (though not when R = alkyl or hydrogen see Chapter 18). Perhaps the best-known rearrangement is that of cyclopropylcarbinyl radicals to a butenyl radical. The rate constant for this rapid ring opening has been measured in... 

As in the case of the base-catalyzed reaction, the thermodynamically most stable alkene is the one predominantly formed. However, the acid-catalyzed reaction is much less synthetically useful because carbocations give rise to many side products. If the substrate has several possible locations for a double bond, mixtures of all possible isomers are usually obtained. Isomerization of 1-decene, for example, gives a mixture that contains not only 1-decene and cis- and franj-2-decene but also the cis and trans isomers of 3-, 4-, and 5-decene as well as branched alkenes resulting from rearrangement of carbocations. It is true that the most stable alkenes predominate, but many of them have stabilities that are close together. Acid-catalyzed migration of triple bonds (with allene intermediates) can be accomplished if very strong acids (e.g., HF—PF5) are used. If the mechanism is the same as that for double bonds, vinyl cations are intermediates. 

This is less common than rearrangement of carbocations, but it does occur (though not when R = alkyl or hydrogen see Chapter 18). 

Besides the rearrangement of carbocations resulting in the formation of isomeric alkylated products, alkylation is accompanied by numerous other side reactions. Often the alkene itself undergoes isomerization prior to participating in alkylation and hence, yields unexpected isomeric alkanes. The similarity of product distributions in the alkylation of isobutane with n-butenes in the presence of either sulfuric acid or hydrogen fluoride is explained by a fast preequilibration of n-butenes. Alkyl esters (or fluorides) may be formed under conditions unfavorable for the hydride transfer between the protonated alkene and the isoalkane. 

Rearrangements of carbocations are among the fastest organic reactions known and must be reckoned with as a possibility whenever carbocation intermediates are involved. 

The rearrangement step (Equation 11-5) is an example of many related rearrangements in which a group, R, migrates with its bonding electrons from one atom to an adjacent atom. We already have encountered an example in the rearrangement of carbocations (Section 8-9B) ... 

We summarize here a procedure to predict the feasibility and the stereochemistry of thermally concerted reactions involving cyclic transition states. The 1,2 rearrangement of carbocations will be used to illustrate the approach. This is a very important reaction of carbocations which we have discussed in other chapters. We use it here as an example to illustrate how qualitative MO theory can give insight into how and why reactions occur ... 

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