Electrophilic addition regiochemistry

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. 

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. 

Problem 13,23 How could you use lH NMR to determine the regiochemistry of electrophilic addition to alkenes For example, does addition of HC) to 1-methylcvclohexene yield 1-chloro-l-methylcyclohexane or l-chloro-2-methylcyclohexane ... 

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. 

Note that if we choose not to put in all the curly arrows, we could write the mechanism in two ways either considering the radical as the attacking species or the double bond as the electron-rich species. The first version is perhaps more commonly used, but it is much more instmctive to compare the second one with an electrophilic addition mechanism (see Section 8.1). The rationalization for the regiochemistry of addition parallels that of carbocation stability (see Section 8.2). 

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. 

It is possible to obtain anti-Markovnikov products when HBr is added to alkenes in the presence of free radical initiators, e.g. hydrogen peroxide (HOOH) or alkyl peroxide (ROOR). The free radical initiators change the mechanism of addition from an electrophilic addition to a free radical addition. This change of mechanism gives rise to the anh-Markovnikov regiochemistry. For example, 2-methyl propene reacts with HBr in the presence of peroxide (ROOR) to form 1-bromo-2-methyl propane, which is an anh-Markovnikov product. Radical additions do not proceed with HCl or HI. 

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... 

Q Use the extended version of Markovnikov s rule to predict the regiochemistry (orien- Problems 8-46, 47, and 50 tation) of electrophilic additions to alkenes. 

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... 

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. 

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