Nucleophilic addition anchimeric assistance

For a number of years, a storm of controversy raged over this proposal, with H. C. Brown as the chief opponent. Brown ruled out anchimeric assistance as an explanation for the rate acceleration of the exo derivative, arguing that exo was normal, but that endo was unusually slow because of a steric effect. The racemization and isotopic tracer results, he proposed, could be explained by a rapid equilibrium between the classical ions 15 and 17 (see Scheme 1.3), with a steric effect responsible for the exo addition of nucleophiles. In terms of the cation, the question revolves around the issue whether the classical ions 15 and 17 should be joined by the equilibrium depiction (the rapidly rearranging scenario) or with a... 

To limit the scope of this review and to reduce overlap with other reviews, some related topics will only be discussed briefly. The addition of salts can affect both the rate and the course of solvolytic reactions and provides very important evidence for ion-pair intermediates. A full discussion of this topic has been published recently (Raber etal., 1974) additional comments are given onpp. 27,32. Also, we have generally excluded solvolyses known to proceed by competitive nucleophilically solvent-assisted and anchimerically assisted pathways. These solvolyses are very common (e.g. even n-propyl tosylate yields 87% of rearranged product during trifluoroacetolysis Reich et al., 1969), but a detailed account has been published recently (Harris, 1974). Recognition that solvolytic reactions could proceed by these two competitive, assisted pathways provided the key to the solution of the controversial phenonium ion problem (Lancelot et al., 1972 Brown et al., 1970), as well as inspiring the reinvestigation of the mechanisms of solvolyses of simple secondary substrates discussed in Section 2. 

Other evidence to support the selection of 2-adamantyl tosylate as model compound has been discussed in Section 2 (p. 8), and the main conclusion can be summarized as follows. Independent evidence and the results in Fig. 15 firmly establish that nucleophilic solvent assistance cannot be appreciable for solvolyses of 2-adamantyl tosylate, since its response to solvents of widely varying nucleophilicities is almost exactly the same as 1-bicyclo [2,2,2] octyl tosylate [49] for which rearside attack is impossible if solvolyses of 2-adamantyl tosylate are anchimerically assisted, the extent of anchimeric assistance does not appear to be dependent on solvent (cf. Pritt and Whiting, 1975). In addition to these conclusions, the results in Fig. 14 suggest that internal return from intermediate contact ion pairs does not occur to a detectable extent for solvolyses of 2-adamantyl tosylate (see also Bentley and Schleyer, 1976). 

The large amounts of five- and six-membered cyclic tosylates, products of internal return (49% yield in one case 12a of Table 3) points also to a highly selective intermediate, although the reason for such a remarkable selectivity towards external nucleophiles is not clear. On the other hand, acetolysis of 6-phenyl-5-hexynyl brosylate, which is apparently anchimerically assisted by the triple bond (4>bs./ caic. = 1 6) yields only the five-membered ring product in addition to open-chain solvolysis products (13 of Table 3). The effect of the phenyl group in orienting the oyclization reaction would indicate that intermediate species like 43 may become important when R =Ph. 

In nonconjugated dienes, the negative inductive effect of the extra double bond reduces the nucleophilicity of the other 7r-system (Fig. 8) [148], There is no evidence for anchimeric assistance by the additional double bond, as observed in certain solvolytic reactions [10,151-153]. When the two double bonds are separated by four methylene groups, they behave as isolated double bonds, and their reactivity equals that of an analogous monoene. 

There is much additional evidence to support the postulate that the effect of neighboring sulfur is due to anchimeric assistance. Cyclohexyl chloride undergoes solvolysis in ethanol-water to yield a mixture of alcohol and ether. As usual for secondary alkyl substrates, reaction is SnI with nucleophilic assistance from the solvent (see Sec. 14.17). A C5H5S— group on the adjacent carbon can speed... 

The bromonium ion in Figure 9.2 was proposed by Roberts and Kimball to explain the stereospecifidty of the addition to alkenes. Independent evidence for the existence of bromonium ions was provided by Winstein and Lucas, who found that ( )-e/yf/iro-3-bromo-2-butanol was converted to mcso-2,3-dibromobutane upon reaction with fuming HBr (equation 9.1), but the ( )-threo reactant formed the ( )-2,3-dibromo-butane. These authors suggested that the bromine provides anchimeric assistance to the departure of the protonated OFI group and forms a bromonium ion which, upon nucleophilic attack by bromide ion, gives a... 

Another widely used comparison, especially in bicyclic systems, is the exojendo rate ratio. This comparison is also fraught with pitfalls. Problems arise because the endo and exo isomers of a polycyclic system have unique configurations and hence different steric requirements. This can affect anchimeric assistance by neighboring groups. In addition there are inherent differences in field effects and nucleophilic solvent assistance. The 350-fold difference in rate constant for acetolysis of exo- and endo-2-norbornyl p-bromobenzenesulfonates [(11) and (12), respectively] was taken as evidence for a participation in the solvolysis of (11) by Winstein... 

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