Regiochemistry eliminations

Hofmann elimination regiochemistry is thought to derive from the steric bulk of the ammonium group that directs deprotonation by base to the least hindered site, leading to formation of the less substituted alkene. 

As the mechanism becomes more ElcB-like, the regiochemistry can start to change. With an E2 reaction that has a lot of carbanion character, the deprotonation of the more acidic hydrogen will dictate the elimination regiochemistry. In ElcB reactions, the regiochemistry is completely dictated by the relative acidity of the protons that can be removed. The double bond will form oriented to the carbon with the most acidic proton. 

Extensive studies on the Wacker process have been carried out in industrial laboratories. Also, many papers on mechanistic and kinetic studies have been published[17-22]. Several interesting observations have been made in the oxidation of ethylene. Most important, it has been established that no incorporation of deuterium takes place by the reaction carried out in D2O, indicating that the hydride shift takes place and vinyl alcohol is not an intermediate[l,17]. The reaction is explained by oxypailadation of ethylene, / -elimination to give the vinyl alcohol 6, which complexes to H-PdCl, reinsertion of the coordinated vinyl alcohol with opposite regiochemistry to give 7, and aldehyde formation by the elimination of Pd—H. 

Butenoic acid and 4-pentenoic acid (42) react with alkenyl halides or tri-flates to afford 7-alkenyl-7-lactones and the ( -alkenyl-5-valerolactone 44 via the TT-allylpalladium intermediate 43 formed by the elimination of Pd—H and its readdition in opposite regiochemistry using a phosphine-free Pd cata-lyst[43]. 

The nature of the transition state in elimination reactions is of great importance, since it controls the regiochemistry of p elimination in compounds in which the double bond can be introduced in one of several positions. These effects are discussed in the next section. 

In the El cb mechanism, the direction of elimination is governed by the kinetic acidity of the individual p protons, which, in turn, is determined by the polar and resonance effects of nearby substituents and by the degree of steric hindrance to approach of base to the proton. Alkyl substituents will tend to retard proton abstraction both electronically and sterically. Preferential proton abstraction from less substituted positions leads to the formation of the less substituted alkene. This regiochemistry is opposite to that of the El reaction. 

Functionalized nitroalkenes are important chenophiles in the Diels-Alder ri example, fE -methyl fi-nitroactylate is an impottant reagent in organic synthesis The nitre group can be readily eliminated the Diels-Alder reaction of fi-nitroactylate is equivalent to that of ethyl propiolate with an inverse regiochemistry fEq. 8.4. ... 

Elimination reactions are more complex than substitution reactions for several reasons. There is, for example, the problem of regiochemistry. What... 

Vinylsilanes react readily with a range of electrophiles to give products of substitution (1). The overall stereochemistry of such substitution will depend on a number of factors, including the stereochemistry of addition and subsequent elimination when 1,2-adducts are discrete species. However, the regiochemistry of substitution is normally unambiguous, the -effect ensuring that carbonium-ion development on attack by the electrophile will occur at the carbon terminus remote, i.e. /3, to silicon ... 

The regiochemistry of this elimination reaction resembles that observed by Davis et al. (see Scheme 9) [23]. The special nature of the bonds in three-mem-bered rings is probably responsible for this exclusive regiochemistry. It is of interest to note that 3,3-dimethylaziridine-2-carboxylic ester indeed leads to the corresponding 3H-azirine ester upon Swern oxidation here there is, of course, no choice. 

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. 

Recall from Chapter 8 that the term regiochemistry refers to where the reaction takes place. In other words, in what region of the molecule is the reaction taking place When H and X are eliminated (where X is some leaving group), it is sometimes possible for more than one alkene to form. Consider the following example, in which two possible alkenes can be formed ... 

However, we must be careful to control the regiochemistry properly in each of these two steps. In the elimination step, we need to form the less substituted double bond (i.e., the Hofmann product), and therefore, we must use a stericaUy hindered base. Then, in the addition step, we need to place the Br on the less substimted carbon (anh-Markovnikov addition), so we must use HBr with peroxides. This gives us the following overall synthesis ... 

Take special notice of what we can accomplish when we use this technique it gives us the power to move the position of a double bond. When using this technique, we must carefully consider the regiochemistry of each step. In the first step (addition), we must decide whether we want a Markovnikov addition (HBr), or an anti-Markovnikov addition (HBr with peroxides). Also, in the second step (elimination), we must decide whether we want to form the Zaitsev product or the Hofmann product (which we can control by carefully choosing our base, ethoxide or fcrf-butoxide). Get some practice with this technique in the following problems. 

There are a few things to keep in mind when using this technique. First of all, radical bromination will selectively place a Br on the most substituted position. Therefore, you should always look for the tertiary position to see where the Br will go. Then, when doing the elimination, make sure to choose the base carefully, in order to achieve the desired regiochemistry. Let s get some practice with this. 

The regiochemistry of the Heck reaction is determined by the competitive removal of the (3-proton in the elimination step. Mixtures are usually obtained if more than one type of (3-hydrogen is present. Often there is also double-bond migration that occurs by reversible Pd-H elimination-addition sequences. For example, the reaction of cyclopentene with bromobenzene leads to all three possible double-bond isomers.146... 

Ruasse and Argile (1983) see Scheme 9 for definition of AdT, AdS, M and kT.6 From kinetics. c From regiochemistry. Elimination products from the tertiary pathway. Elimination products from the secondary pathway. 

Presumably, the oxidative cyclization of 3 commences with direct palladation at the a position, forming o-arylpalladium(II) complex 5 in a fashion analogous to a typical electrophilic aromatic substitution (this statement will be useful in predicting the regiochemistry of oxidative additions). Subsequently, in a manner akin to an intramolecular Heck reaction, intermediate 5 undergoes an intramolecular insertion onto the other benzene ring, furnishing 6. (i-Hydride elimination of 6 then results in carbazole 4. 

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