Alpha-effect nucleophiles

RITCHIE EQUATION ELECTROPHILE NUGLEOPHILIC GATALYSIS NUCLEOPHILIC COMPETITION NUCLEOPHILICITY ALPHA EFFECT ELECTROPHILICITY... 

Nucleophiles alpha effect, 132 hydrazines, 132 hydroxylamines, 132 peroxides, 132... 

Another significant structural effect that inrparts high nucleophilicity is the alpha effect. It is observed that atoms which are directly bonded to an atom with one or rhore unshared pairs of electrons tend to be stronger nucleophiles than would othermse be expected. Examples in Table 5.7 include H02, which is more nucleophilic than HO , and... 

The effects of the nucleophile on aromatic substitution which are pertinent to our main theme of relative reactivity of azine rings and of ring-positions are brought together here. The influence of a nucleophile on relative positional reactivity can arise from its characteristics alone or from its interaction with the ring or with ring-substituents. The effect of different nucleophiles on the rates of reaction of a single substrate has been discussed in terms of polarizability, basicity, alpha effect (lone-pair on the atom adjacent to the nucleophilic atom), and solvation in several reviews and papers. ... 

Although oximes are ambident nucleophiles, a neat regioselectivity allows the formation of oxazolinones. The alpha effect, which is especially relevant for the substimtion of R2C=NO anions at a carbonyl carbon, may offer a good explanation for the Bac2/Bai2 sequence ((9-methoxycarbonylation and A-methylation... 

Enhanced nucleophilicity of an attacking nucleophile attributable to one or more unshared pairs of electrons on an atom that lies immediately adjacent to the nucleophilic group ". The increased nucleophihcity of hydrazines and hydroxylamines is due to an alpha effect, as is the increased nucleophilicity of H02 compared to HO in solution. This effect on nuclephile reactivity can... 

As is also true for ambident anions, substances exhibiting alpha effects in their reactions consistently deviate from the anticipated structure-reactivity correlations known for simple nucleophiles. 

One explanation for the alpha effect is ground-state de-stabilization Repulsive electronic interactions between the alpha atom s lone-pair and the nucleophile occur in the ground-state, and such destabilization is expected to be relieved as a covalent bond is forming in the transition-state of a nucleophilic substitution reaction. Reduced solvation in molecules exhibiting the alpha effect may also play a role in the increased nucleophilicity for example, OH2 displays no effect in the gas phase, but a substantial effect is observed in solution. Another factor may be the abihty of the alpha lone-pair to stabilize any partially positive group formed in the transition state. 

This is an example of what John Edwards and I call the alpha effect. I think it is valuable because it does enable us to generate quite easily a very powerful nucleophilic reagent in water, this hydrogen peroxide anion. 

If, adjacent to the attacking atom on the nucleophile, there is an atom containing one or more unshared pairs, the nucleophilicity is enhanced. Examples of such nucleophiles are H02, Me2C=NO", NH2NH2, etc. This is called the alpha effect,324 and the reasons for it... 

The alpha effect in the SN2 reactions of methyl substrates with three different nucleophiles was shown to correlate with Koopman s theorem ionization potentials for the leaving group.128 This was taken as evidence that (1) the size of the alpha effect in Sn2 reactions depends on the ability of the nucleophile and the leaving group to donate an electron to the methyl group and (2) these transition states have some SET character. The results support the Hoz model129 for the alpha effect. 

Hydroperoxide is a good nucleophile because of the alpha effect interaction of the two lone pairs on adjacent oxygen atoms raises the HOMO of the anion and makes it a better and softer nucleophile than hydroxide. 

If an atom containing one or more unshared pairs is adjacent to the attacking atom on the nucleophile, the nucleophilicity is enhanced. Examples of such nucleophiles are HO2, Me2C=NO, NH2NH2, and so on. This is called the alpha effect (a-effect and a broader definition is a positive deviation exhibited by an a-nucleophile from a Brpnsted type nucleophilicity plot, where the reference (or normal) nucleophile is one that possesses the same basicity as the a-nucleophile, but does not deviate from the Br0nsted-type plot. Several reviews of the a-effect have been published previously, ... 

Several possible explanations have been offered. One is that the ground state of the nucleophile is destabilized by repulsion between the adjacent pairs of electrons another is that the transition state is stabilized by the extra pair of electrons a third is that the adjacent electron pair reduces solvation of the nucleophile. Evidence supporting the third explanation is that there was no alpha effect in the reaction of HOj with methyl formate in the gas phase, although HOj shows a strong alpha effect in solution. The a-efifect has been demonstrated to be remarkably dependent on the nature of the solvent. The a-effect is substantial for substitution at a carbonyl or other unsaturated carbon, at some inorganic atoms, and for reactions of a nucleophile with a carbocation, but is generally smaller or absent entirely for substitution at a saturated carbon. ... 

The origin of the alpha effect is currently a subject for much speculation. Edwards and Pearson (1962) have suggested that, since the nucleophile partially loses two electrons in the transition state (by bonding... 

The alpha-effect is also important in general base-catalyzed nucleophilic reactions, as seen in Fig. 13, where logigb is plotted vs. of the amine, refers to the term second-order in amine in the aminolysis of phenyl acetates in the equation... 

Hydroperoxide is a good nucleophile because of the alpha effect interaction of the two lone pairs on adjacent oxygen atoms raises the HOMO of the anion and makes it a better and softer nucleophile than hydroxide. Hydroperoxide is also less basic than hydroxide because of the inductive electron-withdrawing effect of the second oxygen atom. Basicity and nucleophilicity usually go hand in hand—not here though. This means that the hydroperoxide anion can be formed by treating hydrogen peroxide with aqueous sodium hydroxide. 

Various explanations have been put forth for the alpha effect. One view is that the ground state of the nucleophile is destabilized by lone pair-lone pair repulsions, which decrease in going to the transition state. Another view is that the transition state is stabilized by electron release from the hetero atom. According to this reasoning, the process of bond formation is akin to that of a two-electron transfer ... 

The alpha effect may have a different origin for structurally distinct nucleophiles and it is likely that both electron-pair repulsion and stabilization of the transition state contribute to the overall effect. ... 

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