Radicals, anti-Markovnikov generation

Substituted cyclopropane systems also undergo nucleophilic addition of suitable solvents (MeOH). For example, the photoinduced ET reaction of 1,2-dimethyl-3-phenylcyclopropane (112, R = Me) with p-dicyanobenzene formed a ring-opened ether by anti-Markovnikov addition. The reaction occurs with essentially complete inversion of configuration at carbon, suggesting a nucleophilic cleavage of a one-electron cyclopropane bond, generating 113. The retention of chirality confirms that the stereochemistry of the parent molecule is unperturbed in the radical cation 112 " ". 

Taylor in 1925 demonstrated that hydrogen atoms generated by the mercury sensitized photodecomposition of hydrogen gas add to ethylene to form ethyl radicals, which were proposed to react with H2 to give the observed ethane and another hydrogen atom. Evidence that polymerization could occur by free radical reactions was found by Taylor and Jones in 1930, by the observation that ethyl radicals formed by the gas phase pyrolysis of diethylmercury or tetraethyllead initiated the polymerization of ethylene, and this process was extended to the solution phase by Cramer. The mechanism of equation (37) (with participation by a third body) was presented for the reaction, - which is in accord with current views, and the mechanism of equation (38) was shown for disproportionation. Staudinger in 1932 wrote a mechanism for free radical polymerization of styrene,but just as did Rice and Rice (equation 32), showed the radical attack on the most substituted carbon (anti-Markovnikov attack). The correct orientation was shown by Flory in 1937. In 1935, O.K. Rice and Sickman reported that ethylene polymerization was also induced by methyl radicals generated from thermolysis of azomethane. 

Formation of cycloadducts can be completely quenched by conducting the experiment in a nucleophilic solvent. This intercepts radical cations so rapidly that they cannot react with the olefins to yield adducts. In Scheme 54 the regiochemistry of solvent addition to I-phenylcyclohexene is seen to depend on the oxidizability or reducibiiity of the electron-transfer sensitizer. With ]-cyanonaphthalene the radical cation of the olefin is generated, and nucleophilic capture then occurs at position 2 to afford the more stable radical. Electron transfer from excited 1,4-dimethoxynaphthalene, however, generates a radical anion. Its protonation in position 2 gives a radical that is oxidized by back electron transfer to the sensitizer radical before being attacked by the nucleophilic solvent in position 1. Thus, by judicious choice of the electron-transfer sensitizer, it is possible to direct the photochemical addition in either a Markovnikov (157) or anti-Markovnikov (158) fashion (Maroulis and Arnold, 1979). 

The first step in the mechanism is endothermic and rate determining. The 3° radical produced in anti-Markovnikov attack (A) of bromine radical is several kJ/mole more stable than the 1° radical generated by Markovnikov attack (B). The Hammond Postulate tells us that it is reasonable to assume that the activation energy for anti-Markovnikov addition is lower than for Markovnikov addition. This defines the first half of the energy diagram. 

The other reaction is the peroxide-catalysed addition of HBr to alkenes 7.19 giving the anti-Markovnikov product 7.21. The peroxide generates a bromine radical by abstracting the hydrogen atom from the HBr. The key step is the addition of the bromine atom to the double bond 7.19, which takes place to give the more-substituted radical 7.20, and this in turn abstracts a hydrogen atom from another molecule of HBr to give the primary alkyl bromide 7.21. 

When heteroatom containing substrates react with peroxides, or other radical initiators, hydrogen atom transfer can occur, as in the transfer of hydrogen from an acetal to the radical, generating the alkane and the a-alkoxy radical, 133. The presence of the heteroatom a to the carbon bearing the radical center leads to enhanced stability. Such radicals add to alkenes, usually with anti-Markovnikov orientation, as in the radical... 

Radicals react with alkenes to form a new radical that can react further to give addition reaction products. The initial reaction will generate the more stable radical, and rearrangement is not observed. In the presence of peroxides, alkenes react with HBr to give the alkyl bromide having Br on the less substituted carbon. This is called anti-Markovnikov addition. 

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). 

Anti-Markovnikov addition of phenylseleno radical (generated frombenzeneselenol and catalytic diphenyl diselenide by irradiation with 500 W tungsten lamp in a Pyrex glass tube) to trimethylsilylacetylene furnished a 44% yield of 1 as a 93 7 mixture of E Z isomers(eq 2). ... 

Why does the presence of peroxides cause the addition to be anti-Markovnikov In order to understand the answer to this question, we will need to explore the mechanism in detail. This reaction follows a mechanism that involves radical intermediates (such as Br"), rather than ionic intermediates (such as Br ). Peroxides are used to generate bromine radicals, in the following way ... 

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