Regiochemistry of Electrophilic Additions

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. 

Use Markovnikov s rule to predict the products of HBr addition to the alkenes shown above. 

Is the stable cation that formed as a result of protonation of the more electron-rich end of the alkene Examine electrostatic potential maps for propene, 2-methylpropene and 2-methyl-2-butene. For each, can you tell whether one end of the 7t bond is more electron rich than the other end If so, does protonation on the more electron-rich end lead to the more stable carbocation  

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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 ... 

The Regiochemistry of Electrophilic Addition. Since a symmetrical addend (e.g., Br2, CI2) does not permit a decision to be made regarding which carbon atom in a nonsymmetrical alkene is attacked first (unless solvent or another nucleophile intrudes in the second step), only nonsymmetrical addends such as those in Table 6.1 entries 1-7 and 9-14 (or a symmetrical addend with intrusion of a different nucleophile) can be used to define which end of the double bond (region) receives/ bears which piece of addend. 

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. 

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. 

One possible solution of this problem is to differentiate a radical first as electrophilic or nucleophilic with respect to its partner, depending upon its tendency to gain or lose electron. Then the relevant atomic Fukui function (/+ or / ) or softness f.v+ or s ) should be used. Using this approach, regiochemistry of radical addition to heteratom C=X double bond (aldehydes, nitrones, imines, etc.) and heteronuclear ring compounds (such as uracil, thymine, furan, pyridine, etc.) could be explained [34], A more rigorous approach will be to define the Fukui function for radical attack in such a way that it takes care of the inherent nature of a radical and thus differentiates one radical from the other. 

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... 

Table 11.4 summarizes the reactions in which the electrophile and the nucleophile are linked in the same molecule (hydroboration, hydroxylation, ozonolysis). These additions occur in a concerted manner. The regiochemistry of the addition is such that the nucleophile attaches to the carbon that would be more stable as a carbocation and the addition occurs with syn stereochemistry. 

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. 

Dihalocarbene addition to 24 is related to the addition of carbenes to CgQ, Buckminsterfullerene, which occurs across a Cg-Cg junction to give methanofullerenes, in preference to addition across the fullerene Cg-Cj junction. [58] 2-Adamantanylidene,[58] PhCCl, [58] and CCI2, [59] also behave in this manner. Interestingly, nucleophilic (MeO)2C also attacks a fullerene Cg-Cg junction. [60] Fullerene is a strongly electrophilic substrate, [61] and does not differentiate electrophilic (CCI2) from nucleophilic carbenes on the basis of the regiochemistry of their additions. 

Regiochemistry and stereochemistry of electrophilic additions to allylic double bonds. J Am Chem Soc 109 650-663... 

Addition of bronrine to an alkene is much more complicated than the simple representation in Figure 9.2 would suggest. The classical bromonium ion description of electrophilic addition of bromine to an alkene is useful only as a beginning point to describe the mechanistic options. The structure of the intermediate, the kinetics of the reaction, and both the stereochemistry and the regiochemistry of the products are all complex functions of the nature and concentration of tiie brominating agent, the solvent, any added nucleophiles, and the structure of the alkene. 

The polymerization of alkenes fhen propagates by the electrophilic attack of the carbocation on the double bond of the alkene monomer. The regiochemistry of the addition is determined by the formation of the more stable (the more highly substituted) carbocation. 

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 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. 

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