Neighboring Group Participation

Neighboring group participation (NGP) is also known as anchimeric assistance (Greek: anchi means neighbor), a lone pair of electrons in an atom or the electrons present in a sigma bond or pi bond contained in the parent molecule but not conjugated with the reaction center (so it never be in alpha position) that influences or interacts with a reaction center. Because of the interaction from the neighboring group, (1) the reaction rate can be enhanced, (2) the stereochemical outcomes can be abnormal, and (3) the isomeric products can be isolated (Proust, Gallucci, & Paquette, 2009).

The group is not in alpha position, but it can be positioned either in beta, gamma, or delta position.  Then, by the interaction, they will create 3, 4, 5, or 6-membered rings. Besides that, because of this interaction, the stereochemical outcome is also always retention. It will never proceed with inversion. Therefore, in substitution nucleophilic reaction, it always goes with SN1 or usually called as SN1 anchimeric assistance. 

Below is the mechanism of how NGP interacts with the reaction center. 

Another example:

A paper written by Proust, Galluci, and Paquette (2009) found that substituent para to the sulfonyl protecting groups which act as NGP in a reaction have an influence on nucleophilicity of the sulfonamide nitrogens and the reactivity of the double bond of the diazocines. See the reaction mechanism below:

So, when the substrate has different substituents, there will be 2 possible pathways mean 2 possible products of dibromination. The substituents are various, some are electron withdrawing group such as -NO2, and some others are electron donating group such as -OMe. 

Substrates with different substituents

Two possible products of dibromination

From the table above, electron-withdrawing groups tended to decrease the amount of rearranged dibromides, while electron-donating groups tended to enhance the amount of rearranged dibromide. This is because the nucleophilicity of sulfonamido nitrogen was enhanced by the electron-donating group. Meanwhile, the existence of electron-withdrawing group reduced the nucleophilicity of the nitrogen. It was clearly shown from substrate 8g from entry 7 compared to entry 5 which in entry 5 when both are introduced with electron-donating group, -OMe, the amount of 13 is the highest, but then when one of them is electron-withdrawing group, -NO2, the amount was reduced as the nitrogen nucleophilicity was reduced. 

So, that's how neighboring groups interact with the reaction center and how a substituent in a neighboring group also can influence the reactivity.

That's all from me. I hope it can be useful for you. I apologize if there are any mistakes. Thanks for reading my blog! 

Reference:

Proust, N., Gallucci, J. C., & Paquette, L. A. (2009). Effect of Sulfonyl Protecting Groups on the Neighboring Group Participation Ability of Sulfonamido Nitrogen, (4), 2897–2900.