Nucleophihc catalysis

Keywords Benzoin Carbene NHC Nucleophihc Catalysis Organocatalysis Redox Stetter Transesterification Umpolung... 

Gaseous carbonium ions from the decay of tritiated molecules, 8, 79 General base and nucleophihc catalysis of ester hydrolysis and related reactions, 5, 237... 

Nucleophilic participation is important only for esters of alcohols that have <13. Specifically, phenyl and trifluoroethyl esters show nucleophilic catalysis, but methyl and 2-chloroethyl esters do not. This result reflects the fate of the tetrahedral intermediate that results from nucleophilic participation. For relatively acidic alcohols, the alkoxide group can be eliminated leading to hydrolysis via nucleophihc catalysis ... 

As an example, we can refer to nucleophihc catalysis of hydrolysis ofbenzoate esters by a phosphate buffer (Fig. 5.5), which could be simplified with a two-step sequence (Fig. 5.6). 

In an extensive review on abiotic catalysis, Huang (2000) noted that the reactivity of hydrolyzable organic contaminants arises from the presence of electron-deficient (electrophilic) sites within the molecules. Figures 14.2 and 14.3 show the patterns of reactivity in two cases of nucleophihc substitution and monomolecular nucleophilic substitution. The Sj 2 mechanism (nucleophilic substitution) involves attack of the electrophilic sites by OH" or H O, generation of a higher coordination nnmber intermediate, subsequent elimination of the leaving group, and the formation of an hydrolysis product (Fig. 14.2). 

Over the years, the MNK reaction has emerged as a rehable method, especially for the conversion of aromatic hydroxides into aromatic thiols (and oxidised derivatives). It has received less attention in the aUphatic field because of the existence of alternative methods for transforming alcohols into thiols, namely via ahphatic nucleophihc substitution. Nonetheless, in the aliphatic field, it represents a valuable alternative in the presence of other functional groups and has also been shown to be susceptible to catalysis by a munber of compounds. 

Whether the nucleophile attacks the carbon or the heteroatom attacks the electrophilic species, the rate-determining step is usually the one involving nucleophihc attack. It may be observed that many of these reactions can be catalyzed by both acids and bases.Bases catalyze the reaction by converting a reagent of the form YH to the more powerful nucleophile (see p. 490). Acids catalyze it by converting the substrate to an heteroatom-stabilized cation (formation of 3), thus making it more attractive to nucleophilic attack. Similar catalysis can also be found with metallic ions (e.g., Ag ) which act here as Lewis acids. We have mentioned before (p. 242) that ions of type 3 are comparatively stable carbocations because the positive charge is spread by resonance. 

Under conditions of acid catalysis, the nucleophihc addition step follows protonation of the carbonyl oxygen. Protonation increases the carboca-tion character of a carbonyl group and makes it more electrophilic. 

The nature of the cooperativity was further characterized based on results from kinetic measurements. The two HisH+-His pairs in helix II catalyzed the hydrolysis of mono-p-nitrophenyl fumarate at pH 5.1 and 290 K with second-order rate constants of 0.01 M-i s-i (JNI, His-26, His-30) and 0.055 M s (JNII, His-30, His-34), respectively, and a rate constant ratio JNII/JNI of 5.5. The pKa values of both His residues in JNII are the same, so for the analysis it does not matter which residue is the nucleophile and which one is the acid. In JNI, however, the pKa values are 6.9 for His-26 and 5.6 for His-30. The rate constant ratio of 5.5 should therefore arise due to the difference in nucleophihcity or due to the difference in acidity, or if both residues in the pair can be both nucleophile and acid, from a mixture of the two. If His-30 functions as a general acid in JNI, then the rate constant ratio should arise from the difference in nucleophUicity between two nucleophiles with the pKa values 5.6 and 6.9. We can, however, calculate the reactivity difference as in Section 5.2.3 to find that 10 - = 1.8, one third of the observed ratio of 5.5. If, on the other hand, the rate constant ratio is due to a difference in general-acid catalysis by two residues with pKa values of 5.6 and 6.9, then the the Bronsted equa-hon for general-acid catalysis can be applied... 

As expected from the low hydrogen-bonding ability of sulphur, attempts to observe either intra- or inter-molecular general acid catalysis in the hydrolysis of hemithioacetals have met with little success. The only convincing example is compound LXXIV, in which acid catalysis is concerted with nucleophihc attack by the second carboxylate and contributes a rate enhancement of about 10 [177]. 

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