Regiochemistry of electrophilic additions to alkenes

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 ... 

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. 

Thus, the regiochemistry of hydroboration is predicted by the same general rule that applies to all electrophilic additions to alkenes The reaction of an electrophile with a carbon-carbon double bond occurs preferentially via the transition state in which a partial positive charge develops on that carbon atom better able to accommodate it. Geometric constraints inherent in the cyclic transition state 60 require that the addition of borane to the alkene proceed so that both the boron and the hydrogen add from the same face of the double bond, a process called sy -addition. 

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. 

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. 

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... 

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. 

Electrophilic Addition to Dienes and Polyenes. The tools utilized to examine the reactions of alkenes in Sections 1-3, viz. stereochemistry, regiochemistry, and kinetics, as well as the particular reaction of an alkene with an electrophile in the absence of a reactive nucleophile (i.e., polymerization), can now be applied to the reactions of the same reagents with dienes. In this regard, it should be clear that for isolated dienes or polyenes, that is, alkenes with more than one double bond and in... 

The central topic of this chapter is the addition of HX molecules to alkenes. These reactions begin by the addition of the positive end of the dipole (the electrophile) to the alkene (the nucleophile) in such a way as to form the more stable carbocation. The anion (X ) then adds to the cation to form the final addition product. The direction of addition—the regiochemistry... 

Radicals, lacking a closed outer shell of electrons, are capable of reacting with double bonds. However, a radical requires only one electron for bond formation, unlike the electrophiles presented in this chapter so far, which consume both electrons of the tt bond upon addition. The product of radical addition to an alkene is an alkyl radical, and the final products exhibit anti-Markovnikov regiochemistry, similar to the products of hydroboration-oxidation (Section 12-8). 

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 ... 

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. 

This regiochemistry is consistent with the electrophilic character of Pd(II) in the addition step. Solvent and catalyst composition can affect the regiochemistry of the Wacker reaction. Use of /-butanol as the solvent was found to increase the amount of aldehyde formed from terminal alkenes, and is attributed to the greater steric requirement of /-butanol. Hydrolysis of the enol ether then leads to the aldehyde. 

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. 

It is widely believed that enone-alkene photoadditions proceed through an exciplex (excited complex). For cyclopentenone and 7, the exciplex forms from the photoexcited enone in its triplet state and the glycal in its ground-state. The regiochemistry of addition probably reflects a preferred alignment of the addends in the exciplex. Because a photoexcited enone probably has considerable diradical character, it is reasonable to assume that the more electrophilic a-keto radical would prefer to bind to the more nucleophilic portion of the alkene, since this would maximise attractive interactions within the complex. The reaction of 7 with cyclopentenone would thus favour the formation of diradical 22, which would then ring-close to cyclobutane 14 (Scheme 6.7). 

Earlier in this chapter we noted that nucleophiles attack the CF2 = site in a fluorinated alkene exclusively and, in parallel with these observations, nucleophilic radicals, such as CH3S and carbon-centred radicals, give products arising predominantly from attack at this site (Path 1). Electrophilic radicals such as trifluoromethyl, on the other hand, are less selective and give a mixture of products (Paths 1 and 2) (Eigure 7.58). Examples of the regiochemistry of addition of trifluoromethyl to a variety of fluorinated alkenes are given in Table 7.10. 

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