Neighboring group participation or Anchimeric Assistance
Neighboring group participation (NGP) is a chemical phenomenon that occurs when a reaction center interacts with a lone pair of electrons or electrons in a σ- or π- bond in a molecule. This interaction can increase the rate of the reaction. NGP is also known as anchimeric assistance.
According to the IUPAC, an atom having an unshared pair of electrons and is present on the β– position to the leaving group can act as a neighbouring group. Neighboring group participation is commonly observed in solvolysis reactions where the solvent acts as the nucleophile. For example:
During NGP, the neighbouring group (G) attacks the electrophilic centre to eliminate the leaving group (LG). A cyclic intermediate is formed which is very reactive. The nucleophile (Nu-) then attacks this intermediate to form the product. A common feature of all neighboring group mechanisms is the formation of a cyclic intermediate.
If the attack takes place on the carbon that was having the leaving group then the configuration does not change because the configuration on that carbon inverted twice.
When 2-bromopropanoic acid is treated with dilute alkali, it gives lactate anion with complete retention of configuration. However, with concentrated alkali, (R)2-bromopropanoic acid gives L-lactate anion. This reaction proceeds through inversion of configuration and is a typical SN2 reaction.
Halides, hydroxides, ethers, thio ethers, amino groups, carboxylates, phenyl group, π-bonds etc., have been identified to act as neighbouring groups in many reactions.
NGP by Heteroatom Lone Pairs
NGP by Alkene
The π-orbitals of an alkene are able to stabilize a transition state by helping to delocalize the positive charge of the carbocation. Unsaturated tosylate react about 1000 times faster for aqueous solvolysis with a nucleophile than the saturated tosylate.
The carbocationic intermediate produced is stabilized by resonance when the positive charge spreads over several atoms but no such phenomenon is possible in saturated tosylate
If the alkene is far off from the reacting centre, even then the alkene can still act in this manner.
NGP by Cyclopropane, Cyclobutane or a Homoallyl Group
If Cyclopropylmethyl chloride is made to react with aqueous ethanol, then a mixture of 48% cyclopropylmethyl alcohol, 47% cyclobutanol and 5% homoallyl alcohol (but-3-enol) is formed. This is due to the fact that the carbocationic intermidate is delocalised onto many different carbons through a reversible ring opening.
NGP by Aromatic Rings
The aromatic rings in the β- position can assist as neighbouring groups as was observed in the solvolysis of L-threo-3-phenyl-2-butyltosylate (1) in acetic acid. The reaction produced 96% of the threoacetate product formed as a racemic mixture of (3) and (4) isomers. This can be explained only if the reaction proceeds through the formation of phenonium ion (2) as intermediate. If there had been no involvement of neighbouring group, the erythroproduct (5) would have been obtained. The reactions are shown below.
