Configuration carbocations

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... 

Attack by a nucleophile or the solvent can occur at either of the ion pairs. Nucleophilic attack on the intimate ion pair would be expected to occur with inversion of configuration, since the leaving group would still shield the fiont side of the caibocation. At the solvent-separated ion pair stage, the nucleophile might approach fiom either fece, particularly in the case where solvent is the nucleophile. Reactions through dissociated carbocations should occur with complete lacemization. According to this interpretation, the identity and stereochemistry of the reaction products will be determined by the extent to which reaction occurs on the un-ionized reactant, the intimate ion pair, the solvent-separated ion pair, or the dissociated caibocation. 

Stabilization of a carbocation intermediate by benzylic conjugation, as in the 1-phenylethyl system shown in entry 8, leads to substitution with diminished stereosped-ficity. A thorough analysis of stereochemical, kinetic, and isotope effect data on solvolysis reactions of 1-phenylethyl chloride has been carried out. The system has been analyzed in terms of the fate of the intimate ion-pair and solvent-separated ion-pair intermediates. From this analysis, it has been estimated that for every 100 molecules of 1-phenylethyl chloride that undergo ionization to an intimate ion pair (in trifluoroethanol), 80 return to starting material of retained configuration, 7 return to inverted starting material, and 13 go on to the solvent-separated ion pair. 

More often than what has been mentioned above regarding the cyclization of paraffins over the platinum catalyst, the formed olefin species reacts with the acid catalyst forming a carbocation. Carbocation formation may occur by abstraction of a hydride ion from any position along the hydrocarbon chain. However, if the carbocation intermediate has the right configuration, cyclization occurs. For example, cyclization of 1-heptene over the alumina catalyst can occur by the following successive steps ... 

Aromatization of paraffins can occur through a dehydrocyclization reaction. Olefinic compounds formed by the beta scission can form a carbocation intermediate with the configuration conducive to cyclization. For example, if a carbocation such as that shown below is formed (by any of the methods mentioned earlier), cyclization is likely to occur. 

What about the configuration at C2, the newly formed chirality center As illustrated in Figure 9.16, the stereochemistry at C2 is established by reaction of H20 with a carbocation intermediate in the usual manner. But this carbocation does not have a plane of symmetry it is chiral because of the chirality center at C4. Because the carbocation has no plane of symmetry, it does not react equally well from top and bottom faces. One of the two faces is likely, for steric reasons, to be a bit more accessible than the other face, leading to a mixture of R and 5 products in some ratio other than 50 50. Thus, two diastereomeric products, (2/L4 K)-4-methyl-2-hexanol and (25,4/ )-4-methyl-2-hexanol, are formed in unequal amounts, and the mixture is optically active. 

This lack of complete racemization in most SKd reactions is due to the fact that ioti pairs are involved. According to this explanation, first proposed by Saul Winstein, dissociation of the substrate occurs to give a structure in which the two ions are still loosely associated and in which the carbocation is effectively shielded from reaction on one side by the departing anion. If a certain amount of substitution occurs before the two ions fully diffuse apart, then a net inversion of configuration will be observed Figure 11.11). 

Figure 11.11 Ion pairs in an S l reaction. The leaving group shields one side of the carbocation intermediate from reaction with the nucleophile, thereby leading to some inversion ol configuration rather than complete racemization.

The S il reaction occurs when the substrate spontaneously dissociates to a carbocation in a slow rate-limiting step, followed by a rapid reaction with the nucleophile. As a result, SN1 reactions are kinetically first-order and take place with racemization of configuration at the carbon atom. They are most favored for tertiary substrates. Both S l and S 2 reactions occur in biological pathways, although the leaving group is typically a diphosphate ion rather than a halide. 

For reactions of A-acyliminium ions with alkenes and alkynes one has to distinguish between A-acyliminium ions locked in an s-trans conformation and those which (can) adopt an s-cis conformation. The former type reacts as a (nitrogen stabilized) carbocation with a C —C multiple bond. Although there are some exceptions, the intramolecular reaction of this type is regarded as an anti addition to the 7t-nucleophile, with (nearly) synchronous bond formation, the conformation of the transition state determining the product configuration. 

Like the kinetic evidence, the stereochemical evidence for the SnI mechanism is less clear-cut than it is for the Sn2 mechanism. If there is a free carbocation, it is planar (p. 224), and the nucleophile should attack with equal facility from either side of the plane, resulting in complete racemization. Although many first-order substitutions do give complete racemization, many others do not. Typically there is 5-20% inversion, though in a few cases, a small amount of retention of configuration has been found. These and other results have led to the conclusion that in many SnI reactions at least some of the products are not formed from free carbocations but rather from ion pairs. According to this concept," SnI reactions proceed in this manner ... 

No matter how produced, RN2 are usually too unstable to be isolable, reacting presumably by the SnI or Sn2 mechanism. Actually, the exact mechanisms are in doubt because the rate laws, stereochemistry, and products have proved difficult to interpret. If there are free carbocations, they should give the same ratio of substitution to elimination to rearrangements, and so on, as carbocations generated in other SnI reactions, but they often do not. Hot carbocations (unsolvated and/or chemically activated) that can hold their configuration have been postulated, as have ion pairs, in which OH (or OAc , etc., depending on how the diazonium ion is generated) is the coun-... 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

There is evidence that the configuration of the molecule may be important even where the leaving group is gone long before migration takes place. For example, the 1-adamantyl cation (17) does not equilibrate intramolecularly, even at temperatures up to 130°C, though open-chain (e.g., 5 50 and cyclic tertiary carbocations... 

For example, let s look at the stereochemistry of SnI reactions. We already saw that Sn2 reactions proceed via inversion of configuration. But SnI reactions are very different. Recall that a carbocation is sp hybridized, so its geometry is trigonal planar. When the nucleophile attacks, there is no preference as to which side it can attack, and we get both possible configurations in equal amounts. Half of the molecules would have one configuration and the other half would have the other configuration. We learned before that this is called a racemic mixture. Notice that we can explain the stereochemical outcome of this reaction by understanding the nature of the carbocation intermediate that is formed. 

Remember, an Sn2 mechanism has one step the nucleophile attacks the electrophile, expelling the leaving group. An SnI mechanism has two steps first the leaving group leaves to form a carbocation, and then the nucleophile attacks that car-bocation. Also remember that Sn2 involves inversion of configuration, while SnI involves racemization. Now, try to draw them. 

An essential requirement for such stabilisation is that the carbocation should be planar, for it is only in this configuration that effective delocalisation can occur. Quantum mechanical calculations for simple alkyl cations do indeed suggest that the planar (sp2) configuration is more stable than the pyramidal (sp3) by = 84 kJ (20 kcal) mol-1. As planarity is departed from, or its attainment inhibited, instability of the cation and consequent difficulty in its formation increases very rapidly. This has already been seen in the extreme inertness of 1-bromotriptycene (p. 87) to SN1 attack, due to inability to assume the planar configuration preventing formation of the carbocation. The expected planar structure of even simple cations has been confirmed by analysis of the n.m.r. and i.r. spectra of species such as Me3C SbF6e they thus parallel the trialkyl borons, R3B, with which they are isoelectronic. 

This all suggests slow, rate-limiting breaking of the C—H bond to form the stabilised carbanion intermediate (54), followed by fast uptake of D from the solvent D20. Loss of optical activity occurs at each C—H bond breakage, as the bonds to the carbanion carbon atom will need to assume a planar configuration if stabilisation by delocalisation over the adjacent C=0 is to occur. Subsequent addition of D is then statistically equally likely to occur from either side. This slow, rate-limiting formation of a carbanion intermediate, followed by rapid electrophilic attack to complete the overall substitution, is formally similar to rate-limiting carbocation formation in the SNi pathway it is therefore referred to as the SE1 pathway. 

A proton achieves the valence shell configuration of helium carbocations achieve the valence shell configuration of neon. 

The behavior of members of the bicyclo[2.2.1]heptene family is also different from that of other common 1,2-disubstituted alkenes.230 The parent bicy-clo[2.2.1]heptene gives bicyclo[2.2.1]heptane in only 3.5% yield when it is treated with Et3SiH/TFA. The major product is reported to be a 2-bicyclo[2.2.1]heptyl trifluoroacetate of unspecified configuration (Eq. 70).230 The carbocation intermediate is presumably the 2-norbornyl cation. Addition of small amounts of boron trifluoride etherate to the reaction mixture causes the yield of hydrocarbon product to rise to 22% after a reaction time of 24 hours at room temperature. Further... 

Step 1 is fundamentally an SN2 reaction (kinetics related to structural variations of the reactants,16 8 retention of stereochemistry at phosphorus912), except in those instances wherein a particularly stable carbocation is produced from the haloalkane component.13 A critical experiment concerned with verification of the Sn2 character of Step 1 by inversion of configuration at the carbon from which the leaving group is displaced was inconclusive because elimination rather than substitution occurred with the chiral secondary haloalkane used.14 An alternative experiment suggested by us in our prior review using a chiral primary substrate apparently has not yet been performed.2... 

Moss and coworkers provided an early example of the way in which micellization can control the stereochemical course of a reaction. Deamination of chiral primary aliphatic amines in water proceeds with net inversion and extensive racemization, and the extent of racemization depends upon the lifetime of the carbocation-like intermediate. The situation changes dramatically if the salts of the primary amine can self-micellize, because now the nucleophile, typically water, is directed in from the front-side so that there is extensive retention of configuration (Moss et al., 1973). 

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