Ion-pair intermediates

Studies of the stereochemical course of rmcleophilic substitution reactions are a powerful tool for investigation of the mechanisms of these reactions. Bimolecular direct displacement reactions by the limSj.j2 meohanism are expected to result in 100% inversion of configuration. The stereochemical outcome of the lirnSj l ionization mechanism is less predictable because it depends on whether reaction occurs via one of the ion-pair intermediates or through a completely dissociated ion. Borderline mechanisms may also show variable stereochemistry, depending upon the lifetime of the intermediates and the extent of internal return. It is important to dissect the overall stereochemical outcome into the various steps of such reactions. 

Entry 4 shows that reaction of a secondary 2-octyl system with the moderately good nucleophile acetate ion occurs wifii complete inversion. The results cited in entry 5 serve to illustrate the importance of solvation of ion-pair intermediates in reactions of secondary substrates. The data show fiiat partial racemization occurs in aqueous dioxane but that an added nucleophile (azide ion) results in complete inversion, both in the product resulting from reaction with azide ion and in the alcohol resulting from reaction with water. The alcohol of retained configuration is attributed to an intermediate oxonium ion resulting from reaction of the ion pair with the dioxane solvent. This would react until water to give product of retained configuratioiL When azide ion is present, dioxane does not efiTectively conqiete for tiie ion-p intermediate, and all of the alcohol arises from tiie inversion mechanism. ... 

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. 

The first possibility envisages essentially the same mechanism as for the second-order process, but with Bt2 replacing solvent in the rate-determining conversion to an ion pair. The second mechanism pictures Bt2 attack on a reversibly formed ion-pair intermediate. The third mechanism postulates collide of a ternary complex tiiat is structurally similar to the initial charge-transfer complex but has 2 1 bromine alkene stoichiometry. There are very striking similarities between the second-order and third-order processes in terms of magnitude of p values and product distribution. In feet, there is a quantitative correlation between the rates of the two processes over a broad series of alkenes, which can be expressed as... 

In summary, it appears friat bromination usually involves a charge-transfer complex which collapses to an ion-pair intermediate. The cation can be a carbocation, as in the case of styrenes, or a bromonium ioiL The complex can evidently also be captured by bromide ion when it is present in sufficiently high concentration. 

The stereochemistry of both chlorination and bromination of several cyclic and acyclic dienes has been determined. The results show that bromination is often stereo-specifically anti for the 1,2-addition process, whereas syn addition is preferred for 1,4-addition. Comparable results for chlorination show much less stereospeciftcity. It appears that chlorination proceeds primarily through ion-pair intermediates, whereas in bromina-hon a stereospecific anfi-l,2-addition may compete with a process involving a carbocation mtermediate. The latter can presumably give syn or anti product. 

Ionization is obviously important in the SnI mechanism of nucleophilic substitution, and indeed two ion pair intermediates have been invoked.These are related as in Eq. (8-19), where (s) represents the solvent. 

The ratio of products is not independent of the halide, however, being 68 percent elimination from the chloride and 56 percent from the iodide. The authors conclude that an ion-pair intermediate, which would retain the halide specificity, is responsible for at least part of the reaction. 

The El reactions can involve ion pairs, just as is true for S l reactions (p. 398), This effect is naturally greatest for nondissociating solvents it is least in water, greater in ethanol, and greater still in acetic acid. It has been proposed that the ion-pair mechanism (p. 400) extends to elimination reactions too, and that the S l, Sn2, El, and E2 mechanisms possess in common an ion-pair intermediate, at least occasionally. ... 

Noyori and coworkers found that tetrafluorosilane or trimethylsilyl tri-flate catalyzes the condensation of appropriately protected glycopyranosyl fluorides with trimethylsilyl ethers or alcohols. The strong affinity of silicon for fluorine was considered to be the driving force for this reaction. In the case of Sip4, attack of a nucleophile on the glycosyl cation-SiFj ion-pair intermediate was anticipated. Thus, condensation of 2,3,4,6-tetra-O-benzyl-a- and - -D-glucopyranosyl fluorides (47a and 47fi) with methyl... 

The stereochemistry of addition depends on the details of the mechanism. The addition can proceed through an ion pair intermediate formed by an initial protonation step. Most alkenes, however, react via a complex that involves the alkene, hydrogen halide, and a third species that delivers the nucleophilic halide. This termolecular mechanism is generally pictured as a nucleophilic attack on an alkene-hydrogen halide complex. This mechanism bypasses a discrete carbocation and exhibits a preference for anti addition. 

For S vl attack, considerable charge separation has taken place in the T.S. (cf. p. 81), and the ion pair intermediate to which it gives rise is therefore often taken as a model for it. As the above halide series is traversed, there is increasing stabilisation of the carbocation moiety of the ion pair, i.e. increasing rate of formation of the T.S. This increasing stabilisation arises from the operation of both an inductive effect,... 

This clearly reflects formation of the same, delocalised allylic cation (23, cf. p. 105) as an ion pair intermediate from each halide, capable of undergoing subsequent rapid nucleophilic attack by EtOH at either C, or C3 ... 

Diels-Alder reactions are found to be little influenced by the introduction of radicals (cf. p. 300), or by changes in the polarity of the solvent they are thus unlikely to involve either radical or ion pair intermediates. They are found to proceed stereoselectively SYN with respect both to the diene and to the dienophile, and are believed to take place via a concerted pathway in which bond-formation and bond-breaking occur more or less simultaneously, though not necessarily to the same extent, in the transition state. This cyclic transition state is a planar, aromatic type, with consequent stabilisation because of the cyclic overlap that can occur between the six p orbitals of the constituent diene and dienophile. Such pericyclic reactions are considered further below (p. 341). 

These YA values are found not to run in parallel with the dielectric constant values for the solvents concerned. Obviously the dielectric constant value for the solvent must be involved in some way in YA, as separation of opposite charges is a crucial feature of the rate-limiting step in an SN1 reaction formation of the T.S. leading to the ion-pair intermediate (47). But specific solvation of the separating charges must also be involved and YA will reflect those, and quite possibly other properties of the solvent as well. It is common to describe YA as representing a measure of the ionising power of the solvent A. 

There seems to be no reason why the transition state LXVIII should not be more Stable than the transition state LXVI, just as the corresponding diene is more stable than the other diene. Hence it would be expected that the faster reaction would produce the stable product/ LXX, while in fact LXX is formed only under conditions where an equilibrium ensures that the product will be the more stable isomer. The alternative explanation in terms of a covalent, or at most an intimate ion pair, intermediate thus seems more likely for this particular case. 

Dynamics for the reactions of ion pair intermediates of solvolysis, 39, 1 Dynamics of guest binding to supramolecular systems techniques and selected examples, 42, 167... 

When the sulfenate ROSR is one where R SO- is the anion of a particularly acidic sulfenic acid and R+ is an easily formed carbonium ion, then isomerization to the sulfoxide by a mechanism involving an [R+ OSR l ion pair intermediate becomes possible. Braverman and Svendi (1974) found that on being heated in hexane solution / -methoxybenzyl trichloromethane-sulfenate [25] isomerized rather readily to the corresponding sulfoxide (93). 

Douglass, 1959) to involve an initial nucleophilic attack by the thiolsulfonate on the sulfenyl chloride to give the ion pair intermediate [72] which then yields the products by attack of the chloride ion on the sulfonyl group (184). 

Thus, fluorination of 1,3-dienes proceeds through an allylic ion, while weakly bridged halonium ions are the intermediates in chlorination and bromination of dienes (vide infra). Furthermore, starting from the experimental evidence that 13 is produced under kinetic conditions and not from subsequent rearrangement of the 1,2- and 1,4-adducts, the authors suggested that 13 arose from rearrangement of the allyl cation intermediate, 17. Consistent with an open ion pair intermediate is also the stereoselective formation of the threo isomer from both 1,3-pentadienes, as well as the preference for the addition to the 1,2-bond observed in the reaction of both isomeric pentadienes. This selectivity may indeed... 

Since similar compounds are found in the reaction of the same diene with hydroiodic acid, it has been assumed that the monoiodides were formed by electrophilic addition of HI, which may be due to proton elimination from the first formed ion pair intermediate (equation 80). 

In retrospect, it should have been clear to me - as I am sure it was to Bill Jencks -that the rate and equilibrium constants for addition of solvent to 1-phenylethyl carbocation intermediates of solvolysis of 1-phenylethyl derivatives would serve as the first step in the characterization of the dynamics of the reactions of their ion pair intermediates. Therefore, this earlier work has served as a point of departure for our experiments to determine relative and absolute barriers to the reactions of ion pair intermediates of solvolysis. 

The addition of water to a free carbocation intermediate of solvolysis can be distinguished from addition to an ion-pair intermediate by an examination of common ion inhibition of solvolysis. Common leaving group inhibition of solvolysis is observed when the leaving group ion (X ) acts, by mass action, to convert the free carbocation (R , Scheme 5A) to substrate (R-X). This results in a decrease in the steady-state concentration of R that leads directly to a decrease in the velocity of solvolysis. Some fraction of the solvolysis reaction products form by direct addition of solvent to the carbocation-anion pair intermediate. The external... 

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