Markovnikov additions

The basic premise for making bromosafrole has been to mix sa-frole with Hydrobromic Acid (a.k.a. hydrogen bromide, HBr). That s it. The HBr does what is called a Markovnikov addition reaction whereby the HBr sees the allyl double bond of safrole and preferentially attaches its hydrogen to the gamma carbon and its bromine to the middle beta carbon (don t ask). 

Arylthiols (but not alkylthiols) add to terminal alkynes regioselectively to afford a Markovnikov-type adduct 212 in good yield using Pd(OAc)2 as a catalyst[120]. This result is clearly different from the an/i-Markovnikov addition induced by a radical initiator. The hydroselenation of terminal alkynes with benzeneselenol catalyzed by Pd(OAc)2 affords the terminal alkene 213, which undergoes partial isomerization to the internal alkene 214[121]. 

Addition opposite to Markovnikov s rule is some times termed anti Markovnikov addition... 

Anti Markovnikov addition (Sections 6 8 6 11) Addition re action for which the regioselectivity is opposite to that pre dieted on the basis of Markovnikov s rule... 

A typical example of a nonpolymeric chain-propagating radical reaction is the anti-Markovnikov addition of hydrogen sulfide to a terminal olefin. The mechanism involves alternating abstraction and addition reactions in the propagating steps ... 

The basis of the high normal to isoaldehyde selectivity obtained ia the LP Oxo reaction is thought to be the anti-Markovnikov addition of olefin to HRhCOL2 to give the linear alkyl, Rh(CO)L2CH2CH2CH2CH2, the precursor of straight-chain aldehyde. Anti-Markovnikov addition is preferred ia this... 

Sulfuric acid is about one thousand times more reactive with isobutylene than with the 1- and 2-butenes, and is thereby very useful in separating isobutylene as tert-huty alcohol from the other butenes. The reaction is simply carried out by bubbling or stirring the butylenes into 45—60% H2SO4. This results in the formation of tert-huty hydrogen sulfate. Dilution with water followed by heat hydrolyzes the sulfate to form tert-huty alcohol and sulfuric acid. The Markovnikov addition implies that isobutyl alcohol is not formed. The hydration of butylenes is most important for isobutylene, either directiy or via the butyl hydrogen sulfate. 

Hydration of alkynes (Section 9.12) Reaction occurs by way of an enol intermediate formed by Markovnikov addition of water to the triple bond. 

The reason for its selectivity lies in the insertion step of the cycle. In the presence of the two bulky PPhi groups, the atiachmeni to the mcial of -CH2CH2R (anti-Markovnikov addition, leading to a straight chain product) is easier than the attachment of -CH(CHOR (Markovnikov addition, leading to a branched-chain product). 

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. 

Hydration of an alkene—the addition of water—is carried out by either of two procedures, depending on the product desired. Oxymercuration involves electrophilic addition of Hg2+ to an alkene, followed by trapping of the cation intermediate with water and subsequent treatment with NaBH4. Hydroboration involves addition of borane (BH3) followed by oxidation of the intermediate organoborane with alkaline H202- The two hydration methods are complementary oxymercuration gives the product of Markovnikov addition, whereas hydroboration/oxidation gives the product with non-Markovnikov syn stereochemistry. 

Problem 13.12 We saw in Section 8.3 that addition of HBr to a terminal alkyne leads to the Markovnikov addition product, with the Br bonding to the more highly substituted carbon. How could you use 13C NMR to identify the product of the addition of 1 equivalent of HBr to 1-hexyne ... 

We saw in Section 7.4 that alkenes react with water in the presence of mercuric acetate to yield a hvdroxymercuration product. Subsequent treatment with NaBH4 breaks the C-Hg bond and yields the alcohol. A similar alkoxymercuration reaction occurs when an alkenc is treated with an alcohol in the presence of mercuric acetate or, even better, mercuric trifluoroacetate, (Cl CCtitiHg. Demercura-tion by reaction with NaBH4 then yields an ether. The net result is Markovnikov addition of the alcohol to the alkene. 

Markovnikov addition 85 Matteson reaction 7181 Matteson s reagent 7241 McMurry coupling 17,658,6661, 671... 

The addition of hydrogen halides to simple alkenes, in the absence of peroxides, takes place by an electrophilic mechanism, and the orientation is in accord with Markovnikov s rule. " When peroxides are added, the addition of HBr occurs by a free-radical mechanism and the orientation is anti-Markovnikov (p. 985). It must be emphasized that this is true only for HBr. Free-radical addition of HF and HI has never been observed, even in the presence of peroxides, and of HCl only rarely. In the rare cases where free-radieal addition of HCl was noted, the orientation was still Markovnikov, presumably beeause the more stable product was formed. Free-radical addition of HF, HI, and HCl is energetically unfavorable (see the discussions on pp. 900, 910). It has often been found that anti-Markovnikov addition of HBr takes place even when peroxides have not been added. This happens because the substrate alkenes absorb oxygen from the air, forming small amounts of peroxides... 

The products of the above reactions are consistent with Markovnikov addition of transient Co(Por)H to the unsaturated alkene or alkyne substrate. The regio-chemistry is determined by formation of the most stable organic radical, which... 

Scheme 5.23 Lipase-catalyzed Markovnikov addition of thiols to vinyl esters.

One possibility would be to put the Cl on the less substituted carbon (carbon connected to two other carbon atoms), and the other possibihty would be to put the Cl on the more substituted carbon (carbon connected to three other carbon atoms). If we put the Cl on the more substituted carbon, we call this a Markovnikov addition. If we put the Cl on the less substimted carbon, we call it an anti-Markovnikov addition. How do we know whether we get Markovnikov addition or anti-Markovnikov addition This is an issue of regiochemistry. 

We see that the final position of chlorine is determined by the stability of the intermediate carbocation, which becomes evident as we work through the mechanism. Since chlorine ends up at the more substituted carbon, we call this a Markovnikov addition. The mechanism for this reaction helped explain the regio-chemistry of the reaction. 

Here is where we get back to mechanisms. Whether we are talking about Zaitsev vs. Hoffman elimination reactions or about Markovnikov vs. anti-Markovnikov addition reactions, the explanation of the regiochemistry for every reaction is contained within the mechanism. If we completely understand the mechanism, then we will understand why the regiochemistry had to be the way it turned out. By understanding the mechanism, we eliminate the need to memorize the regiochemistry for every reaction. With every reaction you encounter, you should consider the regiochemistry of the reaction and look at the mechanism for an explanation of the regiochemistry. 

Consider the reaction shown. If you were to add HBr across the double bond, what would the product be Assume a Markovnikov addition. 

---