Nucleophilic aromatic base catalysis

In discussing base catalysis it will prove convenient to adopt, at the outset, a distinction first proposed by Bunnett and Garst22, who noted that the observed cases of catalysis in nucleophilic aromatic substitution could be broadly divided into two categories. The classification was in terms of the relative rates of the catalyzed and uncatalyzed reactions. Since all of the systems could be accommodated empirically by eqn. (4),... 

Schultz and coworkers (Jackson et a ., 1988) have generated an antibody which exhibits behaviour similar to the enzyme chorismate mutase. The enzyme catalyses the conversion of chorismate [49] to prephenate [50] as part of the shikimate pathway for the biosynthesis of aromatic amino acids in plants and micro-organisms (Haslam, 1974 Dixon and Webb, 1979). It is unusual for an enzyme in that it does not seem to employ acid-base chemistry, nucleophilic or electrophilic catalysis, metal ions, or redox chemistry. Rather, it binds the substrate and forces it into the appropriate conformation for reaction and stabilizes the transition state, without using distinct catalytic groups. 

One aspect of asymmetric catalysis has become clear. Every part of the molecule seems to fulfill a role in the process, just as in enzymic catalysis. Whereas many of us have been used to simple acid or base catalysis, in which protonation or proton abstraction is the key step, bifunctional or even multifunctional catalysis is the rule in the processes discussed in this chapter.Thus it is not only the increase in nucleophilicity of the nucleophile by the quinine base (see Figures 6 and 19), nor only the increase in the electrophilicity of the electrophile caused by hydrogen bonding to the secondary alcohol function of the quinine, but also the many steric (i.e., van der Waals) interactions between the quinoline and quinuclidine portions of the molecule that exert the overall powerful guidance needed to effect high stereoselection. Important charge-transfer interactions between the quinoline portion of the molecule and aromatic substrates cannot be excluded. 

The SiiAr2 mechanism of aromatic nucleophilic substitution is theoretically sound and based on experimental evidence, the most decisive of which involves carbocyclic compounds. Strong support for the mechanism has been published by Bunnett and Randall, in particular, the nature of the base-catalysis of the reaction of... 

Reactions involving amine nucleophiles have played an important part in the study of aromatic substitutions, partly because the observation of base catalysis in these reactions provides evidence for the two-step nature of the mechanism. Early work [1 ] on the reactions of aliphatic amines with l-chloro-2,4-dinitrobenzene in ethanol, where nucleophilic attack is rate limiting, showed the importance of steric effects so that, for example, wo-propylamine is roughly 10 times less reactive than n-propylamine. The general pathway for these reactions is shown in Scheme 6.10. Here, the base B may be excess of the nucleophile or added bases such as DABCO or hydroxide ions. The... 

Finally, it is pertinent, in the present connection, to make a distinction between those displacements in which the transformation of reactants to products does not, at any stage, involve the removal of a proton and those which do, at some stage, require the transfer of a proton to a base. The first type is exemplified by reactions with negatively charged nucleophiles such as alkoxide ion, iodide ion or a mercaptide ion or by reactions with tertiary amines or phosphines, which react to form quaternary ammonium compounds or phos-phonium salts, respectively. When the nucleophile is a primary or secondary amine, the product amine, which will have an additional aromatic ring attached to the amine nitrogen, is almost invariably a weaker base than the reactant amine. Here, as will be shown in later discussion, the question of base catalysis, with its attendant complications, arises. 

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