Regiochemistry of addition reactions

In general, five-member ring chelates are formed in preference over six-member ring chelates. Thus, chelation also can be used to control the regiochemistry of addition reactions, as exemplified below. No reduction of the C(4) ester was observed... 

Fig. 5.8. Relationship between small ring structures and regiochemistry of addition reactions.

Reactions of alkynes with electrophiles are generally similar to those of alkenes. Because the HOMO of alkynes (acetylenes) is also of n type, it is not surprising that there IS a good deal of similarity between alkenes and alkynes in their reactivity toward electrophilic reagents. The fundamental questions about additions to alkynes include the following. How reactive are alkynes in comparison with alkenes What is the stereochemistry of additions to alkynes And what is the regiochemistry of additions to alkynes The important role of halonium ions and mercurinium ions in addition reactions of alkenes raises the question of whether similar species can be involved with alkynes, where the ring would have to include a double bond ... 

Phenylmercury halides give the corresponding phenylmercury derivative, CgH5HgC(CF3)3 (61%) [156], and perfluorocyclobutene gives the corresponding cyclobutyl derivative [156], Mechanistically, the reaction could be interpreted as formation of the fluorocarbanion via nucleophilic addition of fluoride ion to the fluoroolefin followed by capture of the intermediate fluorocarbanion by the mercury salt [156]. The regiochemistry of the reaction is consistent with this mechanism [156] (equation 119). 

Here is where we get back to mechanisms. Whether we are talking about Zaitsev vs. Hoffman elimination reactions or about Markovnikov vs. anti-Markovnikov addition reactions, the explanation of the regiochemistry for every reaction is contained within the mechanism. If we completely understand the mechanism, then we will understand why the regiochemistry had to be the way it turned out. By understanding the mechanism, we eliminate the need to memorize the regiochemistry for every reaction. With every reaction you encounter, you should consider the regiochemistry of the reaction and look at the mechanism for an explanation of the regiochemistry. 

We have now seen two pathways for adding HBr across a donble bond the ionic pathway (which gives Markovnikov addition) and the radical pathway (which gives anti-Markovnikov addition). Both pathways are actnally in competition with each other. However, the radical reaction is a mnch faster reaction. Therefore, we can control the regiochemistry of addition by carefully choosing the conditions. If we use a radical initiator, like ROOR, then the radical pathway will predominate, and we will see an anti-Markovnikov addition. If we do not use a radical initiator, then the ionic pathway will predominate, and we will see a Markovnikov addition ... 

Calculations have proven invaluable in understanding the many differences between la and lb. In addition, calculations have provided insight into the substituent effects on the ring expansion reactions of derivatives of lb. Finally, calculations have made predictions about the barriers to and regiochemistries of these reactions. Some of these predictions have been verified others await experimental test. 

Most exohedral fullerene derivatives of preparative importance are formed by one or several successive 1,2-additions to [6,6]-bonds. For a systematic analysis of the regiochemistry of such reactions it is very useful to introduce a simple site labeling system [3]. The relative positional relationships (such as ortho, meta and para in... 

The stereochemistry and regiochemistry of cyclofunctionalization reactions in the following sections are discussed in terms of the above mechanistic concepts. Emphasis is placed on the relationship between the products and the heteroatom-substituted substrates thus, examples of electrophilic heterocycli-zation involving two sequential additions to nonconjugated dienes are not discussed. These reactions have been covered in a recent review. ... 

These E-Z isomerization studies of disilenes indicate that the n overlap between two 3p orbitals of silicon is sufficiently effective to retain the configuration around the double bond, although the 7r bonding of disilenes is significantly weaker than that of the C=C double bond. Therefore, it is expected that if appropriately substituted disilenes can be generated, regiochemistry as well as diastereochemistry of addition reactions to disilenes can be investigated even with transient reactive disilenes. 

Consider the addition of OH and OH across a double bond. We already saw that we don t need to worry about the regiochemistry of this reaction, because we are adding twro of the same group. But what about the stereochemistry ... 

It is widely believed that enone-alkene photoadditions proceed through an exciplex (excited complex). For cyclopentenone and 7, the exciplex forms from the photoexcited enone in its triplet state and the glycal in its ground-state. The regiochemistry of addition probably reflects a preferred alignment of the addends in the exciplex. Because a photoexcited enone probably has considerable diradical character, it is reasonable to assume that the more electrophilic a-keto radical would prefer to bind to the more nucleophilic portion of the alkene, since this would maximise attractive interactions within the complex. The reaction of 7 with cyclopentenone would thus favour the formation of diradical 22, which would then ring-close to cyclobutane 14 (Scheme 6.7). 

Another problem that occurs with eliminations is the regiochemistry of the reaction. As we saw in Chapter 9, most eliminations follow Zaitsev s rule and produce the more highly substituted alkene as the major product. However, a significant amount of the less highly substituted product is also formed. In addition, mixtures of ds and trans isomers are produced when possible, further complicating the product mixture. Because separating a mixture of such isomers is usually a difficult task, elimination reactions are often not the best way to prepare alkenes. (Other methods will be described in subsequent chapters.) However, if only one product can be formed, or if one is expected to greatly predominate in the reaction mixture, then these elimination reactions can be quite useful. 

In some ways the reactions described in this chapter are simpler than those described in Chapter 11. The stereochemistry of the addition is not a concern here because there is no way to determine whether the addition occurs in a syn or an anti manner. Furthermore, the regiochemistry of these reactions is simple the nucleophile always adds to the carbon of the carbonyl group. 

A second metal-catalyzed route to alpha-thioboronate esters consists of the regiospecific, Markovnikov hydroboration of phenyl vinylsulfide which proceeds in high yield to give 14a,b (Equation 11). We are in the process of extending this unique reaction to other alkenyl sulfides and to alkenyl phosphines in order to determin whether the observed regiochemistry of addition is due to a directing effect of the soft heteroatom donor towards the catalyst center. 

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