Neighboring group effects stereochemistry

The cis tosylate cannot assume the diaxial conformation needed for back-side attack by acetoxy, and there is no neighboring group effect. Stereochemistry is normal, and reaction is much slower than for the trans tosylate. 

A cyclic complex derivable by addition of positive bromine to a double bond has already been discussed as an example of the neighboring group effect. The same intermediate, except perhaps for the nature of the bonds to bromine, is formed in the addition of bromine to olefins and is responsible for the stereochemistry of the addition reaction and the nature of the by-products.232... 

On occasion, a molecule undergoing nucleophilic substitution may contain a nucleophilic group that participates in the reaction. This is known as the neighboring group effect and usually is revealed by retention of stereochemistry in the nucleophilic substitution reaction or by an increase in the rate of the reaction. 

This is another example of a neighboring group effect, one that shows itself not in stereochemistry but in rate of reaction. Sulfur helps to push out chloride ion, forming a cyclic sulfonium ion in the process. As fast as it is formed, this intermediate reacts with water to yield the product. 

At least one of the clues to the operation of a neighboring group effect is present in this reaction. The stereochemistry of the product is the opposite to what one would expect from a simple displacement (clue 1). 

The stereochemistry of the reaction also points to neighboring group participation. The product from the optically active exo tosylate is not that of a simple Sn2 reaction, which would be the inverted optically active endo acetate (Fig. 21.51). Instead, it is the product of retention, the exo acetate. We have been alerted to look for just this kind of stereochemical result as evidence of a neighboring group effect— it s clue 1. Moreover, optically active tosylate gives racemic acetate. We will see how this is evidence of an apparent rearrangement, which is clue 2. 

When the 3-bromo-2-butanol with the stereochemical structure A is treated with concentrated HBr, it yields meso-2,3-dibromobutane a similar reaction of the 3-bromo-2-butanol B yields ( )-2,3-dibromobulane. This classic experiment performed in 1939 by S. Winstein and H. J. Lucas was the starting point for a series of investigations of what are called neighboring group effects. Propose mechanisms that will account for the stereochemistry of these reactions. 

It has so far only been possible to solve the complex problem associated with chemical sialylation in a few examples in a convincing way [44]. Due to the lack of a neighboring group at C-3 there is little possibility to influence the stereochemistry at the anomeric center except by solvents. Further, the marked reverse anomeric effect of the carboxyl group leads to the electronically preferred -configuration. Thus, this area would be ideally suited for the apphcation of stereo- and regioselective biocatalysts. 

One concern applicable to all aspects of organic chemistry is the question of the stereochemical outcome of reactions. In the case of C-glycosides, since no anomeric effect exists, the stereochemistry is completely dictated by stereoelectronic effects. Additionally, it should be noted that neighboring group participation is not a predominant factor. The major consequence of these observations is that axially (a) substituted C-glycosides are far more accessible than the corresponding equatorial (p) isomers. 

---