Radical addition, also

Methyl ketones. KMnO mediates the free-radical addition [also in the presence of Mn(OAc)2] of acetone to alkenes in acetic acid, forming methyl ketones in moderate yields. 

We generally think of electrophilic and nucleophilic additions as being heterolytic processes, but there can be electrophilic and nucleophilic character to radical additions also. Alkyl or aryl substituents on a carbonmethyl radical, while electron-withdrawing substituents make it more electrophilic. For a discussion, see Zipse, H. He, J. Houk, K. N. Giese, B. /. Am. Chem. Soc. 1991,113,4324. Perfluoroalkyl radicals are strongly electrophilic see, for example, Avila, D. V. Ingold, K. U. Lusztyk, J. Dolbier, W. R. Pan, H.-Q. /. Am. Chem. Soc. 1993,115,1577. 

B. Radical additions also occur, but they are typically more difficult to control and generally lead to multiple adducts. 

The regioselectivity of addition of HBr to alkenes under normal (electrophilic addi tion) conditions is controlled by the tendency of a proton to add to the double bond so as to produce the more stable carbocatwn Under free radical conditions the regioselec tivity IS governed by addition of a bromine atom to give the more stable alkyl radical Free radical addition of hydrogen bromide to the double bond can also be initiated photochemically either with or without added peroxides... 

The addition of aromatic and aUphatic thiols, RSH and ArSH, and a thioacetic acid to isoprene yields mainly the trans-l,4-adduct (56). The aromatic thiyl radicals, ArS , add almost entirely to the first carbon atom however, aUphatic thiyl radicals, RS, also add to the fourth C atom in significant amounts. 

Interest in synthetic naphthenic acid has grown as the supply of natural product has fluctuated. Oxidation of naphthene-based hydrocarbons has been studied extensively (35—37), but no commercially viable processes are known. Extensive purification schemes must be employed to maximize naphthene content in the feedstock and remove hydroxy acids and nonacidic by-products from the oxidation product. Free-radical addition of carboxylic acids to olefins (38,39) and addition of unsaturated fatty acids to cycloparaffins (40) have also been studied but have not been commercialized. 

This reaction proceeds through a chain mechanism. Free-radical additions to 1-butene, as in the case of HBr, RSH, and H2S to other olefins (19—21), can be expected to yield terminally substituted derivatives. Some polymerization reactions are also free-radical reactions. 

Hexafluoroacetone azine accepts nucleophiles (ROH, RSH, R NH) in positions 1 and 2 to yield hydrazones [27] Phosphites give open-chain products via a skeletal rearrangement [22] Radical addition reactions are also reported [22] Treatment of tnfluoropyruvates with tosylhydrazine and phosphorus oxychlo-ride-pyndme yields tnfluoromethyl-substituted diazo compounds [24] (equation 3)... 

Free-radical addition of hydrogen bromide to the double bond can also be initiated photochemically, either with or without added peroxides. 

Sodium alkanesulfonates for detergent manufacture can also be produced from the free-radical addition of sodium bisulfite and alpha olefins ... 

The same high reactivity of radicals that makes possible the alkene polymerization we saw in the previous section also makes it difficult to carry out controlled radical reactions on complex molecules. As a result, there are severe limitations on the usefulness of radical addition reactions in the laboratory. Tn contrast to an electrophilic addition, where reaction occurs once and the reactive cation intermediate is rapidly quenched in the presence of a nucleophile, the reactive intermediate in a radical reaction is not usually quenched, so it reacts again and again in a largely uncontrollable wav. 

Similar stereoselectivities are achieved in the allylation of enantiomerically pure proline-derived a-oxoamides47. l-Bromo-3-methy]-2-butcne reacts with clean allylic inversion. Since pinacol-type coupling products are also produced under the reaction conditions, this was taken as evidence for a radical addition mechanism47. 

Molecular orbital calculations (ah initio or semiempirical methods) are also often used to provide a description of radical species and their reactions. High levels of theory are required to provide reliable data. However, rapid advances in computer power and computational methods are seeing these methods more widely used and with greater success (for leading references on the application of theory to describe radical addition reactions, see Section 1.2.7). 

Various ab initio and scmi-cmpirical molecular orbital calculations have been carried out on the reaction of radicals with simple alkenes with the aim of defining the nature of the transition state (Section 1.2.7).2I>,j , 6 These calculations all predict an unsymmetrical transition state for radical addition (i.e. Figure 1.1) though they differ in other aspects. Most calculations also indicate a degree of charge development in the transition state. 

Radical additions lo double bonds are, in general, highly exothermic processes and rates increase with increasing temperature. The rcgiospccificity of addition to double bonds and the relative reactivity of various olefins towards radicals are also temperature dependent. Typically, specificity decreases with increasing temperature (the Reactivity-Selectivity Principle applies). However, a number of exceptions to this general rule have been reported. 8 63... 

Various empirical schemes have also been proposed as predictive tools with respect to the outcome of radical addition reactions.9193 Two-parameter schemes, including the Q-e scheme (Section 7.3.4.1), Patterns of Reactivity (Section 7.3.4.2)... 

Halocarbons including carbon tetrachloride, chloroform, bromotrichloroincthane6 (Scheme 6.7) and carbon tetrabromide have been widely used for the production of tclomcrs and transfer to these compounds has been the subject of a large number of investigations." Representative data are shown in Table 6.4. Telomerization involving halocarbons has also been developed as a means of studying the kinetics and mechanism of radical additions.66... 

The above argument is also at odds with the conventional wisdom that the well-known tendency for monomer alternation in copolymerization can primarily be attributed to polar factors. It was suggested9 that, in most cases, radical stabilization could provide an alternate explanation. A discussion on the relative importance of steric polar and radical stabilization effects on radical addition appears in Section 2.3. 

Free-radical addition of Se-phenyl areneselenosulfonates to acetylenes is also a facile process, occurring regiospecifically and stereoselectively to afford the E-isomer of a -(phenylseleno) vinyl sulfone (26) in high yield88. 

A5-hexenyl substituent, extensive cyclization occurs to yield the cyclopentylcarbinyl product from the yields of uncyclized and cyclized products for A5-hexenylmercury chloride, the rate constants for equation 50 have been estimated (vide supra). The SH2 reaction 49 has also been invoked to be the key step in the alkylation of -substituted styrenes by a free-radical addition-elimination sequence, namely96... 

Konig et al. have achieved thioether functionalization of T8[CH = CH2]8 via the radical addition of thiols such as thiophenol, cyclohexylthiol, and 2-mercaptopyridine in the presence of azobisisobutyronitrile (AIBN) as a radical initiator (Table 13), while Gao et al. have also used this method to prepare very highly functionalized POSS by reacting T8[CH = CH2]8 with thiol-terminated glycosides giving glycoclusters in 70% yield (Figure 22). 

The (TMS)3Si radical addition to terminal alkenes or alkynes, followed by radical cyclization to oxime ethers, were also studied (Reaction 50). The radical reactions proceeded effectively by the use of triethylborane as a radical initiator to provide the functionalized pyrrolidines via a carbon-carbon bond-forming process. Yields of 79 and 63% are obtained for oxime ethers connected with an olefin or propargyl group, respectively. 

RSO2, and so on. Addition of Ph3SiSH to terminal alkenes under radical conditions also leads to the primary thiol.With alkynes it is possible to add 1 or 2 mols of RSH. 

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