Stereochemistry nucleophilic substitution reactions

What product would you expect from a nucleophilic substitution reaction of (R)-l-bromo-l-phenylethane with cyanide ion, C=N, as nucleophile Show the stereochemistry of both reactant and product, assuming that inversion of configuration occurs. 

How- does this reaction take place Although it appears superficially similar to the SN1 and S 2 nucleophilic substitution reactions of alkyl halides discussed in Chapter 11, it must be different because aryl halides are inert to both SN1 and Sj 2 conditions. S l reactions don t occur wdth aryl halides because dissociation of the halide is energetically unfavorable due to tire instability of the potential aryl cation product. S]sj2 reactions don t occur with aryl halides because the halo-substituted carbon of the aromatic ring is sterically shielded from backside approach. For a nucleophile to react with an aryl halide, it would have to approach directly through the aromatic ring and invert the stereochemistry of the aromatic ring carbon—a geometric impossibility. 

However, the major factor stimulating the rapid development of static and dynamic sulfur stereochemistry was the interest in the mechanism and steric course of nucleophilic substitution reactions at chiral sulfur. Very recently, chiral organic sulfur compounds have attracted much attention as useful and efficient reagents in asymmetric synthesis. 

The most frequently encountered reactions in organic sulfur chemistry are nucleophilic displacement reactions. The mechanism and steric course of reactions have been the main points of interest of research groups all over the world, in particular, Andersen, Cram, Johnson, and Mislow in the United States Kobayashi and Oae in Japan Kjaer in Denmark and Fava and Montanari in Italy. The results of these investigators have been discussed exhaustively in many reviews on sulfur stereochemistry. In a recent report on nucleophilic substitution at tricoordinate sulfur, the literature was covered by Tillett (10) to the end of 1975. Therefore only some representative examples of nucleophilic substitution reactions at chiral sulfur are discussed here. However, recent results obtained in the authors laboratory are included. 

The mechanistic aspects of nucleophilic substitution reactions were treated in detail in Chapter 5 of Part A. That mechanistic understanding has contributed to the development of nucleophilic substitution reactions as importantl synthetic processes. The SN2 mechanism, because of its predictable stereochemistry and avoidance of carbocation intermediates, is the most desirable substitution process from a synthetic point of view. This section will discuss the role of SN2 reactions in the preparation of several classes of compounds. First, however, the important role that solvent plays in SN2 reactions will be reviewed. The knowledgeable manipulation of solvent and related medium effects has led to significant improvement of many synthetic procedures that proceed by the SN2 mechanism. 

Oil the MCAT, look for carboxylic acid to behave as an acid or as the substrate in a nucleophilic substitution reaction. Like any carbonyl compound, its stereochemistry makes it susceptible to nucleophiles. When the hydroxyl group is protonated, the good leaving group, water, is formed and substitution results. 

After free existence of l-azetin-4-one had been demonstrated, it seems that the mechanism of the so-called nucleophilic substitution reactions of 4-substituted 2-azetidinone follows an elimination-addition pathway. The intermediacy of (1) in displacement reactions is fully consistent with the stereochemistry of the reaction (83CJC1899 91TL2265). 

As we saw in Chapter 8, elimination reactions often compete with nucleophilic substitution reactions. Both reactions can be useful in synthesis if this competition can be controlled. This chapter discusses the two common mechanisms by which elimination reactions occur, the stereochemistry of the reactions, the direction of the elimination, and the factors that control the competition between elimination and substitution. Based on these factors, procedures are presented that can be used to minimize elimination if the substitution product is the desired one or to maximize elimination if the alkene is the desired product. 

Although they really belong in Chapter 17 with other nucleophilic substitution reactions, we included the last few examples of epoxide-opening reactions here because they have many things in common with the reactions of bromonium ions. Now we are going to make the analogy work the other way when we look at the stereochemistry of the reactions of bromonium ions, and hence at the stereoselectivity of electrophilic additions to alkenes. We shall first remind you of an epoxide reaction from Chapter 17, where you saw this. 

There are a number of synthetically important applications, involving these heterocycles, as unstable intermediates, which are reviewed here. These applications feature the ability of selenium to be readily extruded from seleniranes and selenirenes, neighboring group participation by / -Se to control the stereochemistry of nucleophilic substitution reactions, and facile, chemoselective replacement of Se by H in radical-induced reactions. 

Inversion of configuration (Section 7.11C) The opposite relative stereochemistry of a stereogenic center in the starting material and product of a chemical reaction. In a nucleophilic substitution reaction, inversion results when the nucleophile and leaving group are in the opposite position relative to the three other groups on carbon. 

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. 

The stereochemical course of nucleophilic substitution reactions is best illustrated by reference to substitution at a saturated carbon atom. The underlying principles of these reactions are fundamental to an understanding of the more complex stereochemistry of iSn reactions on steroids, carbohydrates and vinyl compounds which are considered in detail in the relevant sections below. 

A mechanism that accounts for both the stereochemistry and the kinet ics of nucleophilic substitution reactions was suggested in 1937 by E. D... 

Micellar control of the stereochemistry of nucleophilic substitution reactions was first recognized in die nitrous acid deamination of 2-aminooctanel91 Below the CMC of 2-octylammonium perchlorate, 2-octanol is formed with the inversion stereochemistry normally expected in the deamination of a 2-aminoalkane. With increasing concentration the percentage of inversion decreases to zero, after which retention of configuration occurs. The observed stereochemistry was demonstrated to... 

Nucleophilic substitution reactions by solvolysis at a carbon atom with a leaving group, Eq. (1), are well enough understood that they are often used in introductory organic chemistry textbooks as an instructional foundation for mechanistic concepts. Information on how variables such as the structure, stereochemistry, the leaving group (LG), and the nucleophilicity of the solvent (SOH) control the reactivity is so extensive that prediction of results for new cases can be made with considerable confidence. 

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