Addition reactions Markovnikov

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). 

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. 

Anti-Markovnikov addition (Sections 6.8, 6.11) Addition reaction for which the regioselectivity is opposite to that predicted on the basis of Markovnikov s rule. 

In addition to the oxymercuration method, which yields the Markovnikov product, a complementary method that yields the non-Markovnikov product is also useful. Discovered in 1959 by H. C. Brown and cailed hydroboration, the reaction involves addition of a B-H bond of borane, BH3, to an alkene to yield an organoborane intermediate, RBH2. Oxidation of the organoborane by reaction with basic hydrogen peroxide, H2O2, then gives an alcohol. For example ... 

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. 

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 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... 

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. 

When you do the same reaction (as above) in the presence of peroxides (R-O-O-R), you get an anti-Markovnikov addition of HBr across the double bond. Draw the product of an anti-Markovnikov addition. 

Do not confuse the concepts of regiochemistry and stereochemistry. For instance, in addition reactions, the term anti-Markovnikov addition refers to the re-giochemistty of the addition, but the term anti refers to the stereochemistry of the addition. Smdents often confuse these concepts (probably because both terms have the word antF). It is possible for an addition reaction to be anti-Markovnikov and a syn addition (hydroboration is an example that you will learn about at some point in time). You must realize that regiochemistry and stereochemistry are two totally different concepts. 

When we explore the mechanisms of addition reactions, we will see why some reactions proceed through a Markovnikov addition while others proceed through an anti-Markovnikov addition. For now, let s make sure that we are comfortable using the terms. 

In other words, we must determine whether the reaction is a Markovnikov addition or an anii-Markovnikov addition. As promised, the answer to this question is contained in the mechanism. In the first step of the mechanism, a proton was transferred to the alkene, to form a carbocation. When starting with an unsymmetrical alkene, we are confronted with two possible carbocations that can form (depending on where we place the proton) ... 

In the previous section, we saw how to add H and X, placing X at the more substituted carbon (Markovnikov addition). There is another reaction that will allow us to add H and X anh-Markovnikov, but it only works well with HBr (not any other H—X). 

In both mechanisms, the regiochemistry is determined by a preference for forming the most stable intermediate possible. For example, in the ionic mechanism, adds to produce a tertiary carbocation, rather than a secondary carbocation. Similarly, in the radical mechanism, Br adds to produce a tertiary radical, rather than a secondary radical, hi this respect, the two reactions are very similar. But take special notice of the fundamental difference. In the ionic mechanism, the proton comes on first. However, in the radical mechanism, the bromine comes on first. This critical difference explains why an ionic mechanism gives a Markovnikov addition while a radical mechanism gives an anti-Markovnikov addition. 

We have now seen two pathways for adding HBr across a donble bond the ionic pathway (which gives Markovnikov addition) and the radical pathway (which gives anti-Markovnikov addition). Both pathways are actnally in competition with each other. However, the radical reaction is a mnch faster reaction. Therefore, we can control the regiochemistry of addition by carefully choosing the conditions. If we use a radical initiator, like ROOR, then the radical pathway will predominate, and we will see an anti-Markovnikov addition. If we do not use a radical initiator, then the ionic pathway will predominate, and we will see a Markovnikov addition ... 

These brackets indicate that H+ is not consumed in the reaction. In other words, H+ is a catalyst, and therefore, we call this reaction an acid-catalyzed hydration. In order to understand why this reaction proceeds via a Markovnikov addition, we turn our attention to the mechanism. The proposed mechanism of an acid-catalyzed hydration... 

A quick glance at the products indicates that we are adding H and OH across the alkene. Let s take a closer look and carefully analyze the regiochemistry and stereochemistry of this reaction. The OH is ending up on the less substituted carbon, and therefore, the regiochemistry represents an anti-Markovnikov addition. But what about the stereochemistry Are we seeing a syn addition here, or is this anti addition ... 

Answer (a) These reagents will accomplish an anti-Markovnikov addition of OH and H. The stereochemical outcome will be a syn addition. But we must first decide whether stereochemistry will even be a relevant factor in how we draw our products. To do that, remember that we must ask if we are creating two new stereocenters in this reaction. In this example, we are creating two new stereocenters. So, stereochemistry is relevant. With two stereocenters, there theoretically could be four possible products, but we will only get two of them we will only get the pair of enantiomers that come from a syn addition, hi order to get it right, let s redraw the alkene (as we have done many times earlier), and add OH and H like this ... 

Answer If we compare the starting material and product, we see that we must add H and OH. We look at the regiochemistry, and we see that OH is ending up at the more substituted carbon—so we need a Markovnikov addition. Then, we look at the stereochemistry and we see that we are not creating two stereocenters in this reaction (in fact, we are not even creating one stereocenter). Therefore, the stereochemistry of the reaction will be irrelevant. So we need to choose reagents that will give a Markovnikov addition of H and OH. We can accomplish this with an acid-catalyzed hydration ... 

The hydrosi(ly)lations of alkenes and alkynes are very important catalytic processes for the synthesis of alkyl- and alkenyl-silanes, respectively, which can be further transformed into aldehydes, ketones or alcohols by estabhshed stoichiometric organic transformations, or used as nucleophiles in cross-coupling reactions. Hydrosilylation is also used for the derivatisation of Si containing polymers. The drawbacks of the most widespread hydrosilylation catalysts [the Speier s system, H PtCl/PrOH, and Karstedt s complex [Pt2(divinyl-disiloxane)3] include the formation of side-products, in addition to the desired anh-Markovnikov Si-H addition product. In the hydrosilylation of alkynes, formation of di-silanes (by competing further reaction of the product alkenyl-silane) and of geometrical isomers (a-isomer from the Markovnikov addition and Z-p and -P from the anh-Markovnikov addition. Scheme 2.6) are also possible. 

The hydroaminations of electron-deficient alkenes with aniline or small primary alkylamines proceed at high conversions (85-95%, nnder mild conditions, 5 mol%, rt), giving exclnsively the anh-Markovnikov addition product. Secondary dialkyl or bnlky primary amines require longer reaction times. With amines containing P-hydrogens, no imine side-products were observed. 

With some secondary amines, especially morpholine, the reaction leads to a mixture of the oxidative amination product and of the hydroamination product, both corresponding to an anh-Markovnikov addition (Eq. 4.39) [166]. 

The stoichiometric hydroamination of unsymmetrically disubstituted alkynes is highly regioselective, generating the azametaUacycle with the larger alkyne substituent a to the metal center [294, 295]. In others words, the enamine or imine formed results from an anti-Markovnikov addition. Unfortunately, this reaction could not be applied to less stericaUy hindered amines. 

In 1993, ten challenges faced the catalysis research community. One of these was the anti-Markovnikov addition of water or ammonia to olefins to directly synthesize primary alcohols or amines [323]. Despite some progress, the direct addition of N-H bonds across unsaturated C-C bonds, an apparently simple reaction, stiU remains a challenging fundamental and economic task for the coming century. 

In 1998, Wakatsuki et al. reported the first anti-Markonikov hydration of 1-alkynes to aldehydes by an Ru(II)/phosphine catalyst. Heating 1-alkynes in the presence of a catalytic amount of [RuCljlCgHs) (phosphine)] phosphine = PPh2(QF5) or P(3-C6H4S03Na)3 in 2-propanol at 60-100°C leads to predominantly anti-Markovnikov addition of water and yields aldehydes with only a small amount of methyl ketones (Eq. 6.47) [95]. They proposed the attack of water on an intermediate ruthenium vinylidene complex. The C-C bond cleavage or decarbonylation is expected to occur as a side reaction together with the main reaction leading to aldehyde formation. Indeed, olefins with one carbon atom less were always detected in the reaction mixtures (Scheme 6-21). 

The addition of hydrogen halide to alkene is another classical electrophilic addition of alkene. Although normally such reactions are carried out under anhydrous conditions, occasionally aqueous conditions have been used.25 However, some difference in regioselectivity (Markovnikov and anti-Markovnikov addition) was observed. The addition product formed in an organic solvent with dry HBr gives exclusively the 1-Br derivative whereas with aq. HBr, 2-Br derivative is formed. The difference in the products formed by the two methods is believed to be due primarily to the difference in the solvents and not to the presence of any peroxide in the olefin.26... 

Recently, on the basis of the Markovnikov addition of water to alkynes, Trost et al. developed a three-component addition reaction of terminal alkynes, water, and methyl vinyl ketone, affording 1,5-diketones in DMF/water in the presence of ruthenium and indium catalysts (Eq. 4.38). 

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