Oxygen nucleophilicity, enhancement

Quantitatively, the enhanced reactivity of hydroxylamine, as well as oximate and hydroxamate ions and also other a-nucleophiles, is expressed as a positive deviation on a Br0nsted-type rate-basicity (pX a) ploh i-e. log k vs pTsTa - This is illustrated in Figure 1 for oxygen nucleophiles and in Figure 2 for nitrogen nucleophiles. It is important to note that the reactivity of the a-nucleophile is considered relative to a normal nucleophile of the same Brpnsted basicity. ... 

Since base catalysis plays an important role in the hydrolytic breakdown of carbamates, this process has been investigated quite extensively. However, very few data are available on the neutral reaction, which, in some cases, may be significant at ambient pH values. The acid-catalyzed reaction, on the other hand, can generally be neglected. This is presumably because so many electron-withdrawing atoms surround the central carbon that protonation of the carboxyl oxygen insignificantly enhances its susceptibility to nucleophilic attack. 

The value of this reaction is enhanced by the fact that the numerous selective transformations of the 2,3-epoxy alcohols at Ct, C2 and C3 with carbon, nitrogen, and oxygen nucleophiles are possible because of electronic and steric factors. 

From the available information it can be concluded that the catalytic apparatus of lipases is similar to that of chymotrypsin (JJ) and other proteinases (Figure 3) (12), A serine oxygen attacks the substrate. The nucleophilicity of this oxygen is enhanced by hydrogen bonding of the... 

The crucial step in this mechanism is the second one in which the a-haloether moiety 115 solvolyzes to give an oxocarbocation. In order to obtain the ionic bicyclobutane this step has to compete effectively with both protonation of the carbanion and the 1,3-elimination reaction. By using oxygen nucleophiles, e.g. MeO", EtO" and CF3CH2O", in pro tic solvents, the rate of these three reactions was found to decrease in the order solvolysis > elimination > protonation. Although an apolar medium is expected to enhance the elimination reaction and to slow down the solvolytic step, it was shown that for MeO" in THF, the ionic bicyclobutane route still prevails. ... 

Trialkyltin alkoxides (86) and dialkylstannylene (87) have recently attracted attention because a tin atom attached to an oxygen atom enhances the nucleophilicity of the latter without increasing its basicity. The synthetic applications of tin alkoxides manifest most remarkably in the case of polyols. For example, 1,2,6-hexanetriol was first stannylated with 1 equiv. of (Bu3Sn)20, followed by treatment with benzoyl chloride giving (88) in 67% yield. Intermediacy of the tributyltin ether (89) was proposed for the regioselective benzoylation (Scheme 35). ... 

Calculations predicted that lone-pair interactions in the (ap, ap) conformation corresponding to )S-glycosides are larger than in the (jc, sc) conformation representing a-glycosides, and thus, the increase of nucleophilicity in the former isomers should be higher. The enhancement of oxygen nucleophilicity can be demonstrated in several, simple reactions. A suitable measure of nucleophilicity of the 0-1 atom is its rate of protonation in... 

The 2,3,3-trimethyl-l-phenyl-l-butanone is an a-substituted ketone, but the a-substituents have no ability to chelate metals. In that case, the role of the Lewis acid will be just to coordinate the oxygen atom, enhancing its reactivity towards the nucleophilic attack. The same open FeUdn-Ahn s model previously commented will be valid for both, TiCU and CeCls-mediated reductions, as it is shown in Scheme 4.4. Again, the first step of the reaction is the coordination of the Lewis acid with the carbonyl group. Although a priori, conformations 9 and 10 could be considered, hydride attack to the carbonyl group in 9 should be favored by steric effects leading to the ti-alcohol 11 as the main reaction product in both cases. 

On the basis of the quantum-chemical studies, it has been established that it is the so called oxyanion hole of the enzyme that binds the carbonyl oxygen or nitrile nitrogen, enhancing the attack of a nucleophile, which is, in turn, activated by histidine (Scheme 5.22) [110]. 

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