Discrete intermediate, nucleophilic substitution

Nucleophilic substitution reactions. The view that substitution or displacement reactions that involve hydroxide ion are examples of polar-group-transfer reactions (with a single-electron shift) is probably the least iconoclastic proposal. Most accept the view that many nucleophilic displacement reactions occur by a SET mechanism.22 In a number of cases free-radical intermediates have been identified, which is consistent with a discrete SET step. Only a slight extension of this concept is required to encompass all nucleophilic reactions within the categories described in Scheme 8-1. 

Structure of the substrate and the reaction conditions determine the transition state for reaction with a particular nucleophile 104, 105). The extreme cases are generally described as the dissociative and associative substitution mechanisms. The fully dissociative mechanism entails the formation of monomeric metaphosphate monoanion as a discrete intermediate and was first formulated by F. H. Westheimer, who pioneered the physical organic chemistry of the hydrolysis of phosphate esters 106, 107). This mechanism is depicted in Eq. (40) and is possible only for phosphomonoesters with good leaving groups, examples of which are shown. 

The main effect of the oxygen atom next to a reaction centre in chemical terms is to stabilise the buildup of positive charge on the central atoms the lone pairs of electrons on the oxygen atom release electrons into the vacant p orbital of an adjacent carbonium ion centre. This means that, compared with nucleophilic substitutions at purely carbon centres, the C—X bond can break to a much greater extent before there is much C—Y bond formation. Indeed, in the limit, for most processes in water the C—X bond completely breaks first and the oxocarbonium ion is a discrete intermediate. 

Knowledge of the contributions of individual substituents to the conformational preferences of oxocarbenium ions, however, is not sufficient to predict the reactivities of highly substituted systems such as those formed from carbohydrates. [Other intermediates, aside from discrete oxocarbenium ions, could also lead to the nucleophilic substitution products. For an example involving ion-pair intermediate, see Crich et al. [15].] For the type of substrates presented in this work, neither the Lewis acid nor the solvent has significant influence upon product distribution as described in Ref. [19]. For instance, although the influences of the C2, C3, and C4 substituents on the mannopyranosyl cation should reinforce each other to favor P-product, a-selectivity was observed upon allylation of the mannosyl phosphate 29 (Fig. 4.10) [Allylation of maimosyl phosphate 29 has been shown to be highly a-selective with MesSiOTf [67]. C-Mannosylation reactions are generally a-selective [68-76]. a-Selectivity was also observed with acetate-protected... 

There are a number of important reactions of aromatic compounds that involve departure of a group with its bonding pair of electrons. Unlike nucleophilic substitution at saturated carbon, aromatic substitution rarely, if ever, involves a single-step reaction instead, discrete intermediates are usually involved. From a synthetic point of view, the aryl diazonium compounds, in which molecular nitrogen serves as the leaving group, are the most important. 

This mechanism explains the observed formation of the more highly substituted alcohol from unsymmetrical alkenes (Markownikoff s rule). A number of other points must be considered in order to provide a more complete picture of the mechanism. Is the protonation step reversible Is there a discrete carbocation intermediate, or does the nucleophile become involved before proton transfer is complete Can other reactions of the carbocation, such as rearrangement, compete with capture by water ... 

The role of the metal ion in ester hydrolysis catalysed by CPA has been examined with both Zn +- and Co +-substituted enzymes. When the terminal carboxyl of the substrate is electrostatically linked to argenine-145 and the aromatic side-chain lies in a hydrophobic pocket, the only residues close enough to the substrate to enter catalysis are glutamate-270, tyrosine-248, the metal ion, and its associated water. Low-temperature studies aid the elucidation of the mechanism. Between - 25 and - 45 °C in ethylene glycol-water mixtures two kinetically discrete processes are detected, the slower of which corresponds to the catalytic rate constant. The faster reaction is interpreted as deacylation of a mixed anhydride acyl-enzyme intermediate formed by nucleophilic attack by glutamate-270 on the substrate (Scheme 6). Differences in the acidity dependences of the catalytic rate constant with the metal ions Zn + (p STa 6.1) and Co +-(pATa 4.9) suggest that ionization of the metal-bound water molecule occurs and is involved in the decay of the anhydride. The catalytic rate constant shows an isotope effect in DgO. 

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