Ambident SN2 Nucleophiles

Molecules that possess more than one nucleophilic si are referred to as ambident nucleophiles. Sn2 reactioi involving these nucleophiles may lead to mixtures i products. For example, nucleophilic attack by nitrite c methyl bromide gives both nitromethane and methyl nitrit 

Examine atomic charges and the electrostatic potential nu for nitrite anion. Which atom(s) is most electron riel Which product would be obtained if this atom behav as a nucleophile in its reation with methyl bromide. 

Other possible ambident nucleophiles include cyanii anion (CN ), methyl sulfinate anion (CH3SO2 ), ar acetone enolate (CH3COCH2 ). Identify the most electro rich atom(s) in each anion (based on charges alone), ar indicate the major product that should result from an S, reaction with methyl bromide at this atom(s). 

Another way to assess nucleophilic reactivity is to examii the shape of the nucleophile s electron-donor orbital (th is the highest-occupied molecular orbital or HOMC Examine the shape of each anion s HOMO. At which ato would an electrophile, like methyl bromide, find the be orbital overlap (Note This would involve overlap of tl the HOMO of the nucleophile and the lowest-unoccupif molecular orbital or LUMO of CH3Br.) Draw all of tl products that might result from an Sn2 reaction wi CHaBr at these atoms. 

Can the ambident nucleophilicity of any of these anioi be explained solely on electrostatic grounds Solely ( orbital overlap grounds Explain your reasoning. 

---

Second, and as discussed in Part A, Chapter 5, nucleophilicity in Sn2 reactions is associated with polarizability. The more easily a nucleophile s electronic cloud can be distorted to permit bond formation, the stronger an Sn2 nucleophile it will be. Comparison of the oxygen and carbon ends of an ambident enolate ion with regard to nucleophilicity leads to the conclusion that the less electronegative carbon atom is more polarizable and to the prediction that the carbon end of the anion will be more nucleophilic. 

Moreover, reactions at side chain centers, such as Sn2 displacement49-51 and attack on an ester carbonyl,50-52-53 may compete or prevail. Further complexity may result from the presence of ambident nucleophiles.5455... 

These results clearly show that the potential energy surface can contain a series of minima. The fact that selectivity in re-attack by the F ions can be observed indicates that the differences between the energy barriers for the secondary reactions control the distribution of the final products. The multistep character of these processes is further illustrated by the reactions observed when enolate anions are used as reactant ions. The ambident enolate anions may react with methyl pentafluorophenyl ether at the carbon or the oxygen site. If they react with the carbon site at the fluorine-bearing carbon atoms, then the molecule in the F ion/molecule complex formed contains relatively acidic hydrogen atoms so that proton transfer to the displaced F ion may occur. An example is given in (47) where the enolate anion, generated by HF loss, is not observed. An intramolecular nucleophilic aromatic substitution occurs instead and leads to a second F ion/ molecule complex. The F" ion in this complex then re-attacks the substituted benzofuran molecule formed, either by proton transfer or SN2 substitution. 

Kornblum s rule As the nature of a reaction changes from SN1 to SN2, an ambident nucleophile becomes more likely to attack with its less electronegative atom. 

---