Radical addition regiochemistry

Other radicals can add to alkenes, and the rate constant for the addition of methyl radicals to alkenes has been studied,and the rate of radical additions to alkenes in general has also been studied.The kinetic and thermodynamic control of a radical addition regiochemistry has also been studied. Alkynes... 

The regiochemistry of methyl radical attack (CH3) to a series of substituted ethylenes (Scheme 12.6) [33]. Generally, the radical attack occurs at the less substituted end of of the olefins. It has been found that while there is no correlation between the global softness (5) for radicals and the barrier heights for radical addition, the barrier tends to decrease with the increase in electronegativity of the radicals. 

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. 

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. 

In the presence of peroxides, hydrogen bromide adds to the double bond of styrene with a regioselectivity opposite to Markovnikov s rule. The reaction is a free-radical addition, and the regiochemistry is governed by preferential formation of the more stable radical. 

Table 5. Regiochemistry of trifluoromethyl radical additions to olefins [85,92,93]...

The reversal of the regiochemistry of addition is the result of the reversal of the order in which the two components add to the alkene. Radical addition leads to the formation of the more stable... 

Wojciechowski G, Ortiz de Montellano PR (2007) Radical energies and the regiochemistry of addition to heme groups. Methylperoxy and nitrite radical additions to heme of horseradish peroxidase. J Am Chem Soc 129 1663-1672... 

The anti-Markovnikov addition of HBr to alkenes was probably the first free-radical addition reaction to be discovered. The discovery was inadvertent around the turn of the twentieth century, scientists studying the regiochemistry of addition of HBr to alkenes found that the proportion of Markovnikov to anti-Markovnikov addition products varied inexplicably from run to run. Eventually, it was discovered that impurities such as O2 and peroxides greatly increased the amount of anti-Markovnikov addition product. The results were later explained by a free-radical addition mechanism. The anti-Markovnikov regiochemistry derives from the addi-ton of the Br- radical to the less substituted C of the alkene (steric reasons) to give the lower energy, more substituted radical (electronic reasons). In a polar reaction, Br- would add to the more substituted C of the alkene. 

This polar mechanism is in contrast to the non-polar radical mechanism for the addition of hydrogen bromide that we will study in the next section. We will see that the radical mechanism gives rise to addition with the //7//-Markovnikov regiochemistry. There is a further difference between the polar and the non-polar reactions, in that the radical addition is usually syn in nature, assuming that the radical has a short half life, while, as we have seen, the polar reaction is usually anti in nature. 

Radical addition is usually syn in nature, and awfr-Markovnikov in regiochemistry. This result is often called the peroxide effect, because peroxides are often used as the radical initiator. 

The first propagation step in the addition chain is a radical addition. The second propagation step in the addition chain is a radical abstraction. Radical addition of HBr is a typical reaction. Bromine radical adds to the multiple bond to form the most stable of the possible radicals. The radical addition of HBr gives the opposite regiochemistry of addition as the polar addition of HBr. 

Use radical stabilities to predict the regiochemistry of the radical addition chain reaction of HBr to propene (initiated by AIBN). 

The regiochemical outcome of a radical addition to substituted alkenes generally depends on a complex blend of bond strength, polarity and steric effects . The more common result is the attack on the less substituted carbon. Recently Shaik and Canadell used a state correlation diagram (SCO) model to derive the regiochemical trends in radical addition to substituted alkenes. Regiochemistry was discussed in terms of the relative spin density in the state of the alkene (which directs the radical... 

The addition of fhe bromine afom to the alkene could occur at either C of the double bond, but it is dominated by addition that gives the more stable radical. In the mechanism just described, the two choices are the formation of a primary or tertiary radical. Because a tertiary carbon radical is more stable than a primary radical, the regiochemistry ends up as non-Markovnikov. Recall that the polar addition of HBr to an alkene is regioselective (Section 6.3A), with bromine adding to the more substituted carbon (Markovnikov addition). There is an important similarity between the polar mechanism (Section 6.3A) and the radical mechanism. The regiochemistry of each reaction is dominated by the reactions that proceed through the most stable reactive intermediates, which are in both cases tertiary, as shown below. This pair of alkene additions illustrates how the products of a reaction often can be altered by... 

In Chapter 9, we saw that the regiochemistry of ionic addition of HBr is determined by the tendency to proceed via the more stable carbocation intermediate. Similarly, the regiochemistry of radical addition of HBr is also determined by the tendency to proceed via the more stable intermediate. But here, the intermediate is a radical, rather than a carbocation. To see this more... 

Intermolecnlar Additions. The radical chain nature and the anti-Markovnikov regiochemistry of radical addition reactions were originally discovered by Kharasch in the 1930s. Since then, these reactions have been used extensively for the formation of carbon-carbon and carbon-heteroatom bonds. Substrates that are suitable for the former include polyhalomethanes, alcohols, ethers, esters, amides, and amines. The prototypical examples compiled in Table 1 are from reviews by Walling and Ghosez et al. ... 

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). 

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