Stereochemistry of electrophilic addition reactions

Before we examine the stereochemistry of electrophilic addition reactions, we need to become familiar with some terms used in describing the stereochemistry of a reaction. 

Section 5.19 Stereochemistry of Electrophilic Addition Reactions of Alkenes... 

Now that you are familiar with electrophilic addition reactions and with stereoisomers, we can combine the two topics and look at the stereochemistry of electrophilic addition reactions. In other words, we will look at the stereoisomers that are formed in the electrophilic addition reactions that were discussed in Chapter 4. 

We will begin our discussion of the stereochemistry of electrophilic addition reactions by looking at reactions that form a product with one asyimnetric center. Then we will look at reactions that form a product with two asyimnetric centers. 

The effects of the cr—JT interaction on the ground-state properties of allyltrimethylmetal compounds are paralleled by the effect on reactivity towards electrophilic reagents. Mayr demonstrated that allyltrialkylsilanes, allyltrialkyl-germanes, and trialkylstannanes react with diphenylcarbenium ions at rates 105,5.6 x 105, and 109, respectively, relative to propene.158 The reaction rates were also found to be sensitive to the inductive effects of the other substituents attached to the metal. A theoretical evaluation of the factors determining the regiochemistry and stereochemistry of electrophilic addition to allylsilanes and other allyl systems is reported by Hehre et al.159 They predict a preference for electrophilic attack anti with respect to the silane substituent, a prediction that is supported by many experimental studies.82,160... 

The stereochemistry of electrophilic addition to norbornenes and norbomadienes is very interesting" . As these reactions form on intermediate carbocations, there arises, just as for the solvolysis of 2-substituted norbornanes and norbornenes, the question of the nature of these ions — classical or nonclassical. The electrophilic addi-... 

The bromonium ion postulate, made more than 75 years ago to explain the stereochemistry of halogen addition to alkenes, is a remarkable example of deductive logic in chemistry. Arguing from experimental results, chemists were able to make a hypothesis about the intimate mechanistic details of alkene electrophilic reactions. Subsequently, strong evidence supporting the mechanism came from the work of George Olah, who prepared and studied stable... 

The Lead-Off Reaction Addition of HBr to Alkenes Students usually attach great-importance to a text s lead-off reaction because it is the first reaction they see and is discussed in such detail. 1 use the addition of HBr to an alkene as the lead-off to illustrate general principles of organic chemistry for several reasons the reaction is relatively straightforward it involves a common but important functional group no prior knowledge of stereochemistry or kinetics in needed to understand it and, most important, it is a polar reaction. As such, 1 believe that electrophilic addition reactions represent a much more useful and realistic introduction to functional-group chemistry than a lead-off such as radical alkane chlorination. 

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

The reaction proceeds smoothly and gives 326 in 43% yield. The stereochemistry of the addition is exo with respect to the norbomene moiety and in line with the usual cycloaddition behavior of quadricyclane [358]. The norbomene double bond in 326 is easily accessible by electrophiles, and, for example, the anti-addition of benzenesulfenyl chloride proceeds quantitatively at room temperature (Scheme 4.66). 

With ions or dipolar substrates, radical ions undergo nucleophilic or electrophilic capture. Nucleophilic capture is a general reaction for many alkene and strained-ring radical cations and may completely suppress (unimolecular) rearrangements or dimer formation. The regio- and stereochemistry of these additions are of major interest. The experimental evidence supports several guiding principles. 

Figure 6.1. Summary of the most common electrophilic addition reactions of olefins. In each case, the olefin reacts as a Lewis base. All reactions are regioselective. The overall stereochemistry is (a) stereospecific anti (b) stereospecific syn (c) not stereospecific, in general.

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. 

The full paper on the reactions of iodine(l) thiocyanate and 5a-androst-2-ene and other alkenes has appeared." An investigation into the stereochemistry of the addition of BrCl to cholesterol revealed that the ratio of a /8 attack was 4.5 1, which was higher than that for other electrophilic additions. It was suggested that the reaction involved rapid reversible formation of the bromonium ions followed by attack by chloride ion and that the opening of the 5/8,6/3-bromonium ion was slow relative to that of the 5a,6a-bromonium ion owing to steric interactions with the la-, 3a-, 7a-, and 9a-axial hydrogen atoms. 

Androst-is-en-iy-ones (9) readily add methanol, hydrogen cyanide, etc., with stereospecific i5j8-attachment (10) of the nucleophile [265]. The stereochemistry of conjugate addition to both Ai -20-ketones and A S-i -ketones follows the same pattern as for electrophilic attack upon the A - and A -enolic derivatives respectively of 17-0x0- and 16-0x0 steroids (p. 167). AU these reactions probably depend upon a combina-... 

In addition, the lithium enolate derived from pseudoephedrine propionamide has been shown to undergo highly diastereoselective Mannich reactions with p-(methoxy)phenyl aldimines to form enantiomerically enriched a,p-disubstituted p-amino acids (Table 10). As observed in alkylation reactions using alkyl halides as electrophiles, lithium chloride is necessary for the reaction of aldimines. With respect to the enolate, the stereochemistry of the alkylation reactions is the same as that observed with... 

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