Markovnikov regiochemistry

Figure 7.3 Mechanism of the oxymercuration of an alkene to yield an alcohol. The reaction involves a mercurinium ion intermediate and proceeds by a mechanism similar to that of halohydrin formation. The product of the reaction is the more highly substituted alcohol, corresponding to Markovnikov regiochemistry.

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

Alkynes don t react directly with aqueous acid but will undergo hydration readily in the presence of mercury(II) sulfate as a Lewis acid catalyst. The reaction occurs with Markovnikov regiochemistry the -OH group adds to the more highly substituted carbon, and the — H attaches to the less highly substituted one. 

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. 

NMR can be used to help identify the product of nearly every reaction run in the laboratory. For example, we said in Section 7.5 that bydroboration/oxidation ol alkenes occurs with noo-Markovnikov regiochemistry to yield the less highly substituted alcohol. With the help of NMR, we can now prove this statement. 

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. 

Step 3 of Figure 27.14 Third Cyclization The third cationic cyclization is somewhat unusual because it occurs with non-Markovnikov regiochemistry and gives a secondary cation at C13 rather than the alternative tertiary cation at C14. There is growing evidence, however, that the tertiary carbocation may in fact be formed initially and that the secondary cation arises by subsequent rearrangement. The secondary cation is probably stabilized in the enzyme pocket by the proximity of an electron-rich aromatic ring. 

Stabilize a neighboring, empty p-orbital, so too, alkyl groups can stabilize a neighboring, partially filled orbital. This preference for forming a tertiary radical (rather than a secondary radical) dictates that Br" will attack the less substituted carbon. This explains the observed anti-Markovnikov regiochemistry. 

Careful comparison of the starting material and prodnct will reveal that we have performed a hydration, with Markovnikov regiochemistry. Notice the reagent that we used (H3O+). Essentially, this is water (H2O) and an acid sonrce (such as sulfuric acid). There are many ways to show this reagent. Sometimes, it is written as H3O+ (as above), while at other times, it might be written like this H2O, H+. You might even see it like this, with brackets around the acid ... 

To recap, the reaction above is an addition of H and OH, with anti-Markovnikov regiochemistry, and syn stereochemistry. Now we have three important questions to answer ... 

Oxymercuration/demercuration provides a milder alternative for the conventional acid-catalyzed hydration of alkenes. The reaction also provides the Markovnikov regiochemistry for unsymmetrical alkenes.33 Interestingly, an enantioselective/inverse phase-transfer catalysis (IPTC) reaction for the Markovnikov hydration of double bonds by an oxymercuration-demercuration reaction with cyclodextrins as catalysts was recently reported.34 Relative to the more common phase-transfer... 

When a nucleophile reacts with a bromonium ion, the addition takes place with Markovnikov regiochemistry. 

Nucleophile reacts with bromonium ions II or III at the carbon of each that bears the greater positive charge, in accord with Markovnikov regiochemistry. 

Electron transfer sensitization allows either the radical cation or the radical anion of an aromatic alkene to form as desired, which finally results in nucleophile addition with Markovnikov and anti-Markovnikov regiochemistry. In an apolar solvent, the tight radical ion pair undergoes a stereoselective reaction when the electron-accepting sensitizer is chiral (Figure 3.10). ... 

If the fi C—X bond is free to rotate away from periplanarity, then fi C—H bonds will adopt the geometry reqnired for hyperconjugation [as shown for carbocation (6)] and Markovnikov regiochemistry will be favoured. The results are consistent with ab initio theoretical calculations and can be rationalized using a simple electrostatic model."... 

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. 

Click Coached Tutorial Problems for more practice in Predicting Markovnikov Regiochemistry. 

I 1.48 Explain why this reaction occurs with anti-Markovnikov regiochemistry ... 

Carbon-Carbon Hydrogen Halides Predicting Markovnikov Regiochemistry (page 412)... 

Strategy Hydroboration/oxidation occurs with non-Markovnikov regiochemistry to give products in which -OH is bonded to the less highly substituted carbon. 

Addition of one equivalent of HX or X2 to a triple bond occurs with Markovnikov regiochemistry to yield a product in which the two added atoms usually have a transrelationship across the double bond. 

Markovnikov regiochemistry is observed, yielding the more highly substituted alcohol. 

Hydrogen bromide, HBr Adds to alkenes with Markovnikov regiochemistry to yield alkyl bromides (Sections 6.7 and 14.2). 

Markovnikov regiochemistry occurs, w ith H adding to the less highly substituted alkene carbon and halogen adding to the mote highly substituted carbon. 

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