Radicals, anti-Markovnikov halides

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... 

Free-Radical Addition. Free-radical attack on a butylene occurs so that the most stable radical carbon structure forms. Thus, in peroxide-catalyzed addition of hydrogen halides, the addition is anti-Markovnikov. 

Another method for preparing alkyl halides involves a reaction without car-bocation or anion intermediates. The reaction involves radical intermediates, so the mechanism of this process is quite different from those seen previously. The reaction of an alkene with HBr in the presence of a peroxide gives an anti-Markovnikov bromide, as discussed in Chapter 10, Section 10.2. That reaction involves a radical intermediate. 

Retrosynthetic analysis of nitrile 164 disconnects the C-CN bond because it is clear that the six carbons of the methylcyclopentene starting material are more or less intact in the remainder of the molecule. This disconnection requires a C-C bond-forming reaction involving cyanide. Because cyanide is associated with a carbon nucleophile, assign Cj to the cyanide and to the cyclopentene carbon. The synthetic equivalent for Cg is an alkyl halide, and 2-bromo-l-methylcyclopentane (168) is the disconnect product. Bromide 168 is obtained directly from the alkene starting material, but it requires the use of a radical process to generate the anti-Markovnikov product (see Chapter 10, Section 10.8.2). 

Electrophilic addition of HCl or HBr to an alkene normally occurs with Mar-kovnikov regiochemistry, resulting in an alkyl halide with the halogen located at the more substituted carbon of the starting alkene. Since the presence of peroxides (ROOR) initiates a radical mechanism, HBr can also be added to an alkene with anti-Markovnikov orientation. Anti addition of bromine or chlorine to an alkene gives a trans-dibromo or dichloro product. 

This transformation begins with the anti-Markovnikov, radical addition of HBr to give a primary alkyl halide. This bromide undergoes an Sn2 displacement with acetylide to give the desired TM (the acetylide anion is commercially available, or it can be prepared from acetylene). 

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