Neighboring group effect intramolecular

Rearrangements and neighboring group effects intramolecular nudeopldlic attack... 

Studies of vinyl polyelectrolyte solutions connected with problems of this type have dealt with specific effects of neighboring groups in intramolecular reactions and rates of reaction between polyelectrolytes and simple substrates. Comprehensive reviews of this subject have been published (27, 22, 23). 

Boucher apfdied the same approach to the calcidation of tl kinetics of intramolecular reactions with neighboring-group effects Introducing three rate constants ko> ki, kj, as in the case of polymeranalogous reactions, he obtained the following equations ... 

Selective deacetylation of the C-4 acetate of taxol or baccatin III proved to be a challenging task because this acetate group is in a very hindered location. The first clue to a method for selective deacetylation came in studies of the hydrolysis of hexahydrobaccatin III 58) in which it was found that hexahydrobaccatin III itself underwent reasonably selective deacylation at C-10 and C-4 to give the 4,10-bis-deacetyl derivative. A 13-(triethylsilyl)-analog, however, underwent selective hydrolysis at the C-10 and C-2 positions. These results were explained by a neighboring group effect, with intramolecular transfer of the C-4 acetate to the C-13 position. 

The term intramolecular catalysis introduced by Bender is also widely used to describe neighboring group effects, especially when analogous intermolecular catalysis is observed. Thus this term is commonly used when referring to reactions that are subject to acid, base, and/or nucleophilic catalysis such as hydrolysis of esters, amides, and acetals the mutarotation of aldoses or the enolization of ketones. It is rarely used when referring to nucleophilic substitution reactions at saturated carbon. 

In its simplest form, the study of neighboring group effects notes that a heteroatom with a pair of nonbonding electrons can act as a nucleophile in an intramolecular displacement reaction, just as external nucleophiles can participate in intermolecu-lar S]v2 reactions. In an example we have seen (p. 317), oxiranes can be formed from halohydrins in base (Fig. 21.2). 

Other reactions are more subtle than these straightforward intramolecular processes, but there are always clues when a neighboring group effect is involved. For example, consider the reaction of the optically active a-bromocarboxylate in methyl alcohol (Fig. 21.4). 

Whenever you see an unexpected stereochemical result (usually retention where inversion is expected), look for an intramolecular displacement reaction—a neighboring group effect. You will almost always find it. 

There are three clues that point to the operation of a neighboring group effect. The first is an unusual, often backward stereochemical result. Generally, this involves retention of configuration when inversion might have been anticipated. The second is formation of an unexpected product that appears to be the result of a rearrangement. The unexpected product arises because an intermediate is formed that can react further in more than one way. The third clue is an unexpected increase in the rate of a reaction. The anchimeric assistance provided by an intramolecular nucleophile often reveals itself in the form of a rate increase. 

The formation of the wrong stereoisomer is the clue to the operation of a neighboring group effect in the reaction of Figure 21.21. The product is formed not with the inversion of configuration required by the mechanism, but with retention (clue 1). After the hydroxyl group is protonated, it is displaced not by an external bromide ion, but by the bromine atom lurking in the same molecule (Fig. 21.22). It is most important at this point to keep the stereochemical relationships clear. Displacement must be from the rear, as this is an intramolecular Sn2 reaction. 

PROBLEM 21.52 The animation titled Intramolecular Sn2 is a nice example of a neighboring group effect. Select that reaction and observe the process. Is the starting material in a boat or a chair conformation Does the S]s 2 process occur from the more stable chair structure Why or why not ... 

Scheme 3.57 Neighboring group effects on the diastereoselectivity of samarium(ll) iodide mediated intramolecular reductive 1,4-additions.

Abstract The structure/reactivity behavior for pure hydrocarbon diene monomers, and for dienes containing heteroatoms has been examined. Steric hindrance is the controlling factor for hydrocarbon monomers, and intramolecular electronic interactions determine the reactivity of dienes possessing heteroatom functionality. This electronic interaction phenomenon is termed the "Negative Neighboring Group Effect". 

The reactions and compound presented in this chapter support the notion that the formation of o-QMs from the parent phenols is a quite complex process. In the case of the oxidation by Ag20 but also likely in other oxidations, a zwitterionic intermediate is involved that can be stabilized intermolecularly, for example, by electrostatic interaction with other suitable zwitterions, or intramolecularly by neighboring groups or inductive/mesomeric effects. By stabilizing the zwitterionic intermediate and destabilizing the o-QM, the energetic gap between these two intermediates is lowered and... 

The effective concentrations of nucleophiles in intramolecular reactions are often far higher than this. The examples that follow are for unstrained systems. The chemist can synthesize compounds that are strained the relief of strain in the reaction then gives a large rate enhancement. In the succinate and aspirin derivatives that follow, the attacking nucleophile can rotate away from the ester bond to relieve any strain. The observed rate enhancements are due entirely to the high effective concentration of the neighboring group ... 

Depending on the relative gains and losses in internal rotation, the intramolecular reaction is favored entropically by up to 190 J/deg/mol (45 cal/deg/mol) or 55 to 59 kJ/mol (13 to 14 kcal/mol) at 25°C. Substituting 190 J/deg/mol (45 cal/deg/mol) into the exp (ASVR) term of equation 2.7 gives a factor of 6 X 109. Taking into account the difference in molecularity between the second-order and first-order reactions, this may be considered as the maximum effective concentration of a neighboring group, i.e., 6 X 109 M. In other words, for B in equation 2.22 to react with the same first-order rate constant as A B in equation 2.23, the concentration of A would have to be 6 X 109 M. 

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