Neighbouring-group substitution

A neighbouring-group participation mechanism prevents the immediate nucleophilic substitution of iodine by a second equivalent of benzoate that would lead to a syn-substituted product Instead, a cyclic benzoxonium ion intermediate is formed ... 

How do we know that neighbouring group participation is taking place Well, the first bit of evidence is the increase in rate. The neighbouring groups will become involved only if they can increase the rate of the substitution reaction—otherwise the mechanism will just follow the ordinary S 2 pathway. But more important information comes from reactions where stereochemistry is involved, and one of these is the last of the four examples above. Here it is again in more detail. Not only does the first of these reactions go faster than the second—its stereochemical course is different too. 

Neighbouring group participation is impossible, and substitution goes simply by intermolecular displacement of OTs by AcOH. Just one S 2 step means overall inversion of configuration, and no participation means a slower reaction. ... 

If you see a substitution reaction at a stereogenic saturated carbon atom that goes with retention of stereochemistry, lookfor neighbouring group participation ... 

You ve already met the most important ones—sulfides, esters, carboxylates. Ethers and amines (you will see some of these shortly) can also assist substitution reactions through neighbouring group participation. The important thing that they have in common is an electron-rich heteroatom with a lone pair that can be used to form the cyclic intermediate. Sulfides are rather better than ethers—this sulfide reacts with water much faster than rc-PrCl but the ether reacts with acetic acid four times more slowly than rc-PrOSC Ar. 

The Mitsunobu reaction is one of the staple reactions for clean nucleophilic substitution with inversion of configuration. It came as a surprise, therefore, to find that a Mitsunobu reaction on atlyEic alcohol 143,1 [Scheme 8 143) using terf-butyl 2-(trimethylsilyl)ethylsulfonylcarbamate (143.2) as the nucleophile occurred with retention of configuration.320 The unusual stereochemistry was explained by a double inversion process in which neighbouring group participation first leads to the intermediate 1433. A subsequent second nucleophilic substitution by 1433 then gave the product 143.4 in 86% yield ... 

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