Elimination Reactions—Regiochemistry and Stereochemistry

We have mentioned many times that you need to think about the regiochemistry and stereochemistry of every reaction. We will now consider those issues for elimination reactions, beginning with regiochemistry. 

Regiochemistry refers to where the reaction takes place. In other words, in what region of the molecule is the reaction taking place When you eliminate H and X (where X is some leaving group), it is possible to form the double bond in different locations. Consider the following simple example  

Where does the double bond form This is a question of regiochemistry. The way we distinguish between these two possibilities is by considering how many groups are attached to each double bond. Double bonds can have anywhere from l to 4 groups attached to them  

if we look back at the reaction above, we find that the two possible products are monosubstituted and disubstituted double bonds. Whenever you have an elimination reaction where more them one possible double bond can be formed, we have names for the different products based on which one is more substituted and w hich one is less substituted. The more substituted product is called the Zaitsev product, and the less substituted product is called the Hoffmann product. Usually you get the Zaitsev product, but under special circumstances you can get the Hoffman product. If you use a strong, sterically hindered base, you can form the Hoffman product. 

PROBLEM 10.28 Search through your textbook, find the section that covers formation of Hoffmann products, and then draw the structures of the sterically hindered bases that your textbook show s you. 

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The major focus in this chapter will be on synthesis, with emphasis placed on more recent applications, particularly those where regiochemistry and stereochemistry are precisely controlled. The reader is referred to the earlier reviews for full mechanistic information and details of historic interest. Electrophilic addition of X—Y to an alkene, where X is the electrophile, gives products with functionality Y (3 to the heteroatom X. Further transformations of X and/or Y provide the basis for diverse synthetic applications. These transformations include replacement of Y by hydrogen, elimination to form a ir-bond (either including the carbon bonded to X or (3 to that carbon so that X is now in an allylic position), and nucleophilic or radical substitution. Representative examples of these synthetic methods will be given below. This chapter will include examples of heterocycles formed in one-pot reactions where the the initial alkene-electrophile adduct contains an electrophilic group that can react further. Examples of heterocycles formed in several steps from alkene-electrophile adducts will also be considered. Cases in which activation by an external electrophile directly results in addition of an internal heteroatom nucleophile are treated in Chapter 1.9 of this volume. 

For the reaction above run in basic water, draw an ElcB elimination mechanism and explain the regiochemistry and stereochemistry found. 

Bottom line How should you study addition reactions For every addition reaction that you encounter, you must draw the mechanism first. Once you completely understand it, then you can look for the stereochemistry and regiochemistry and try to justify them based on the mechanism. Then you will be in a position to understand any of the factors that your textbook mentions about that reaction. Those factors will often help you determine when and how quickly the reaction occurs. There will usually be fewer factors than we saw in substitution and elimination reactions. Usually only one or two factors will be covered on any reaction (if even that). You should then turn to the end of Chapter 8 and summarize this information for each reaction. You will record the mechanism and the key information regarding stereochemistry and regiochemistry. If you repeat this process for every reaction that you learn (not just addition reactions, but all reactions), then you will be in really good shape. 

Follow the steps listed in the preceding Visual Summary of Key Reactions section. Identify the leaving group, the electrophilic carbon, and the nucleophile (or base). Then determine which mechanism is favored (see Section 9.7). Watch out for stereochemistry where important, regiochemistry in elimination reactions, and carbocation rearrangements when the mechanism is SN1 or El. 

Organocuprates and a few other carbon nucleophiles sometimes react with allylic halides (or acetates) to give the product of what looks like an SN2 reaction. However, the mechanism is completely different— preliminary coordination by the copper or other transition metal to the C=C n bond is the first step, and the coordination of the copper changes from rj-2 to rj-1 or rj-3 before a reductive elimination step establishes the C—C bond.394 Each of these steps affects the overall regiochemistry (and the stereochemistry discussed in the next chapter), which may look like an SN2 or an SN2 reaction, while mechanistically being neither. 

Chapter 5 considers the relationship between mechanism and regio- and stereoselectivity. The reactivity patterns of electrophiles such as protic acids, halogens, sulfur and selenium electrophiles, mercuric ion, and borane and its derivatives are explored and compared. These reactions differ in the extent to which they proceed through discrete carbocations or bridged intermediates and this distinction can explain variations in regio- and stereochemistry. This chapter also describes the El, E2, and Elcb mechanisms for elimination and the idea that these represent specific cases within a continuum of mechanisms. The concept of the variable mechanism can explain trends in reactivity and regiochemistry in elimination reactions. Chapter 6 focuses on the fundamental properties and reactivity of carbon nucleophiles, including... 

Show the expected products, including stereochemistry and regiochemistry, of any elimination reaction. 

For some elimination reactions only one product is possible. For others, there may be a choice of two (or more) alkene products that differ either in the location or stereochemistry of the double bond. We shall now discuss the factors that control the stereochemistry (geometry) and regiochemistry (i.e., where the double bond is) of the alkenes, starting with El reactions (Scheme 2.16). 

As p-hydride elimination is reversible, hydropalladation with the opposite regiochemistry provides a mechanism for forming regioisomers of the alkene. This allows the most stable alkene that is accessible by the hydropalladation-dehydropalladation sequence to dominate. The only restriction is that all of these processes are syn. The migration can be prevented by the addition of bases like silver carbonate, which effectively removes the hydrogen halide from the palladium complex as soon as it is formed. This synthesis of a complex trans dihydrofuran involves the Heck reaction followed by alkene isomerization and then a Heck reaction without migration to preserve the stereochemistry. 

One other experimental result from the Corey et al. study is important for trisubstituted alkene synthesis. When 55=58 is quenched with formaldehyde, the stereochemistry of C—C bond formation remains the same as before. However, the regiochemistry of the elimination step no longer favors the second aldehyde added, and the major product is now the allylic alcohol 64 (54). This experiment suggests that both oxaphosphetanes 63 and 62 are in equilibrium with the lithium halide adduct 61a. Decomposition is controlled by the nature and degree of oxaphosphetane substitution as well as by stereochemistry. In the formaldehyde reaction, these factors combine to favor the trisubstituted alkene (via 62) over the disubstituted alkene that would be formed via 63 (R"=H). Several examples of trisubstituted alkene synthesis using Corey s method are summarized in Table 10 without further comment because the origins of stereochemistry are not understood in detail, but Corey s model 58 is consistent with the available evidence. 

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