Intramolecular induced nucleophilic catalysi

Induced intramolecular nucleophilic catalysis involves the formation of a molecular addition complex (Ad) between the reactant/substrate (R-A) and catalyst (W-B) followed by intramolecular nucleophilic substitution reaction between two reaction sites A and B giving products P3 and P4, where one of the products, say P4, is unstable, i.e., more reactive, and, hence, P4 undergoes further reaction to reproduce catalyst (W-B) and give the final stable product P5. This whole chemical process may be shown by Equation 2.27. Intramolecular induced nucleophilic catalysis involves the intermolecular nucleophihc substitution reaction between R-A and catalyst, (C-W-B), where nucleophilicity of the nucleophile is enhanced owing to intramolecular interaction between molecular sites B and C of catalyst. 

Induced Intramolecular Nucleophilic Catalysis Nature s most efficient catalysts often bring about the maximum possible reduction in the overall free energy of activation for both simple and extremely complex reactions. The molecular machinery involved in reactions of these catalysts is fascinating and awesome, and gives rise to the idea of designing synthetic catalysts that could mimic some, if not all, the characteristic molecular features of Nature s catalysts. Perhaps, this is the fastest way to come up with an efficient catalyst for a specific purpose. In order to synthesize such a cost-effective catalyst, it is essential to know the fine details of the mechanism of the reaction catalyzed by Nature s catalyst. This aspect of such effort is indeed extremely difficult, if... 

Occasionally, the presence of boric acid in the reaction mixture increases the rate of reaction because of the change in the nature of reaction from intermolecular reaction to intramolecular reaction owing to complex formation between the reactant and boric acid. Such rate enhancement is sometimes described as induced catalysis. This terminology is correct only if boric acid has lower (compared to the reactant) or no binding or reaction affinity with the products. When products react or complex with boric acid with the same or greater affinity as with the reactants, then such a rate enhancement is more correctly described as boric-acid-induced intramolecular nucleophilic reaction. 

Another mode for metal ion catalysis of phosphoryl transfer is by complexation with a nucleophile of the form R-OH, thereby facilitating its deprotonation to form the more nucleophilic alkoxide or hydroxide. An example is the catalysis of the aqueous hydrolysis of phosphorylated pyridines by Mg(OH) +. 71 A rate enhancement of 104 was attributed to the greater nucleophilicity of the metal-bound hydroxide relative to water. A further rate enhancement of 102 was attributed to induced intramolecularity arising from interaction of the metal ion with both the hydroxide nucleophile and the nonbridge phosphoryl oxygens in the transition state.71... 

There is little effect of micelles upon the rate of an intramolecular nucleophilic reaction. Micelles of hexadecyltrimethylammonium bromide catalyse, by factors of 10 —10, the arenesulphinate anion-induced hydrolysis of 4-tolylsulphonyl-methyl perchlorate. There is no relationship between the rate acceleration and hydro-phobicity of the sulphinate anion and catalysis is attributed to the concentration of the reactants in the micellar phase.The rate constants for the reaction of nucleophiles with carbonium ions and those for the addition of cyanide ion to the A -alkylpyridinium ions are similar in the micellar and aqueous phases, and the rate enhancement is due to the concentration of reactants in the micellar pseudophase. Similarly, although micellar catalysed dephosphorylation by nucleophiles may show rate enhancements of up to 4 x 10 -fold, the second-order rate constants may be slightly smaller in the micellar pseudophase lowing to its lower polarity. However, the reaction of fluoride ion with 4-nitrophenyldiphenyl phosphate is very rapid in micelles of cetyltrimethylammonium fluoride, but the rate constant continues to increase when the substrate is fully bound with increasing cetyltrimethylammonium fluoride or sodium fluoride. The failure of the micellar pseudophase model is also apparent in the reaction of hydroxide ion with 2,4-dinitrochlorobenzene. It is suggested that reaction occurs between reactants in the aqueous and micellar pseudophases and also between hydroxide ion in water and substrate in the micelle. ... 

Induced Intramolecular and Intramolecular Induced Nucleophilic Catalysis... 

Reports on the rate enhancements in intramolecular nucleophilic reactions compared to analogous intermolecular nucleophilic reactions are plenty. But such reports on induced intramolecular or intramolecular induced nucleophilic catalysis are rare. One might argue that the induced intramolecular/intramolecular induced nucleophilic reactions also represent the corresponding nucleophilic catalysis. But this statement is not totally correct in view of the definition of a catalyst. For example, hydroxide-ion-catalyzed second-order rate constant (koe) for the cleavage of one of the two amide bonds in N,N-dimethylphthalamide (13) at 25.3°C is 7.6 sec. The value of koe for the cleavage of amide bond in... 

Design of Enomine-Cyclization Cascade Reactions The nucleophilic Y in intermediate 6 can react with other electrophiles intermolecularly (Scheme 1.34a) or intramolecularly (Scheme 1.34b) as well as with the iminium ion. Moreover, the carbonyl group of 6 can also undergo intramolecular aldol reaction with nucleophilic X (Scheme 1.34c). These nucleophilic addition reactions after enamine catalysis induce cyclization reactions to produce versatile five- or six-membered ring structures. 

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