Electrophilic addition reactions regiochemistry

Markovnikov s rule is used to predict the regiochemistry of HX (electrophilic) addition reactions. The rule states that HX adds to an unsymmetrical alkene mainly in the direction that bonds H to the less substituted alkene carbon and X to the more substituted alkene carbon. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

One of the most striking differences between conjugated dienes and typical alkenes is in their electrophilic addition reactions. To review briefly, the addition of an electrophile to a carbon-carbon double bond is a general reaction of alkenes (Section 6.7). Markovnikov regiochemistry is found because the more stable carbo-cation is formed as an intermediate. Thus, addition of HC1 to 2-methylpropene yields 2-chloro-2-methylpropane rather than l-chloro-2-methylpropane, and addition of 2 mol equiv of HC1 to the nonconjugated diene 1,4-pentadiene yields 2,4-dichloropentane. 

Markovnikov s rule (Section 6.8) A guide for determining the regiochemistry (orientation) of electrophilic addition reactions. In the addition of HX to an alkene, the hydrogen atom bonds to the alkene carbon thal has fewer alkyl substituents. 

Mechanism of the o] mercuration of an alkene to yield an alcohol. TTiis electrophilic addition reaction involves a mercurinium ion intermediate, and its mechanism is similar to that of halohydrin formation. The product of the reaction is the more highly substituted alcohol, corresponding to Markovnikov regiochemistry. 

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 ... 

The silyl and stannyl substituents are crucial to these reactions in two ways. In the electrophilic addition step, they act as electron-releasing groups promoting addition and also control the regiochemistry. A silyl or starmyl substituent strongly stabilizes carboca-tion character at the /3-catbon atom and thus directs the electrophile to the a-carbon. The reaction is then completed by the limination step, in which the carbon-sihcon or carbon-tin bond is broken. 

One general, and as yet unsolved problem, is understanding and predicting the regiochemistry of arylnitrenium ion addition to DNA bases. This reaction is complicated because phenylnitrenium ion has four potential sites of addition (Fig. 13.21) the nitrenium center as well as the ortho and para ring carbons. Likewise, DNA has numerous sites for electrophilic addition. In guanine bases alone, there is a possibility for addition to N7, 06, N2, or C8. 

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. 

While the regiochemistry of simple electrophilic additions to double bonds is controlled by a combination of electronic (Maikovnikov rule), stereoelectronic (trans diaxial addition to cyclohexenes) and steric factors,9 the intramolecular nature of electrophilic heteroatom cyclizations introduces additional conformational, stereoelectronic and entropic factors. The combination of these factors in cyclofunctionalization reactions results in a general preference for exo cyclization over endo cyclization (Scheme 4).310 However, endo closure may predominate in cases where electronic or ring strain factors strongly favor that mode of cyclization. The observed regiochemistry may differ under conditions of kinetic control from that observed under conditions of thermodynamic control. 

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... 

This chapter presented many reactions. Although most of them follow the same general mechanism in which an electrophile adds to the carbon-carbon double bond, there are several variations on this mechanism. In addition, the regiochemistry and/or the stereochemistry of the reaction may be important. Complications, such as carbocation rearrangements, may occur. You will have an easier time remembering all these details if you organize the reactions according to the three variations of the mechanism that they follow. 

Aromatic compounds undergo many reactions, but relatively few reactions that affect the bonds to the aromatic ring itself. Most of these reactions are unique to aromatic compounds. A large part of this chapter is devoted to electrophilic aromatic substitution, the most important mechanism involved in the reactions of aromatic compounds. Many reactions of benzene and its derivatives are explained by minor variations of electrophilic aromatic substitution. We will study several of these reactions and then consider how substituents on the ring influence its reactivity toward electrophilic aromatic substitution and the regiochemistry seen in the products. We will also study other reactions of aromatic compounds, including nucleophilic aromatic substitution, addition reactions, reactions of side chains, and special reactions of phenols. 

Selenenyl chlorides add to alkenes, often via an AdE2 mechanism involving a bridged seleniranium ion intermediate (19) (equation 14). These reactions are therefore highly stereospecitic, resulting in anti addition. The regiochemistry of the process can be under either kinetic or thermodynamic control. In some cases, initial anti-Markovnikov products were observed at low temperature and Markovnikov adducts dominated after further equilibration. Analogous electrophilic additions to acetylenes and aUenes (Scheme 9) have also been reported. When selenenyl hahdes react with alkenes in the presence of other nucleophiles such... 

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