Radical Additions to Unsaturated Systems

For the reaction of hydroxyl radical with organic species, there are three common reaction pathways (a) hydroxyl radical addition to unsaturated systems (e.g., double bonds), (b) hydrogen abstraction (typically from alkyl or hydroxyl groups), and (c) direct electron transfer. These generic mechanisms are illustrated in Figure 1. For nonradical reactants, all three mechanisms result in initial products that are radicals. Subsequent reactions follow to yield nonradical products. Additional reactants are necessary to complete these subsequent reactions. Common reactants include Fe2+, Fe3+, 02, H20, H+, HO, other metals, other organics, and other radicals present in the system. Dimerization can also occur if the initially formed radical species reacts with... 

Anodic oxidation of the nitroalkane anion to a radical may lead to dimerization [22], addition to unsaturated systems [23], or substitution in aromatic compounds [24] these reaactions are treated in Chapter 22. 

Unsaturated fatty compounds such as oleic acid [la], 10-undecenoic acid [2a], pet-roselinic acid [3a], erucic acid [4a], and the respective esters, alcohols, and native oils (Fig. 1) are alkenes and contain an electron-rich double bond that can be functionalized in many different ways by reactions with electrophilic reagents. It is therefore remarkable that >90% of oleochemical reactions have been focused on the carboxylic acid functionality and < 10% have been reactions of the alkyl chain and the C,C-dou-ble bond (1). A review on radical additions to unsaturated fatty compounds that appeared in 1989 (2) quoted only very few C,C-bond-forming reactions giving branched and chain-elongated fatty compounds. Since then, modem preparative radical chemistry has been developing and has been applied also to fat chemistry (3-5). We report here on radical additions of activated haloalkanes such as alkyl 2-haloalka-noates and 2-haloalkanenitriles to unsaturated fatty compounds [l]-[4] initiated by electron transfer from copper in solvent-free systems. These additions were also car-... 

The addition of radicals and, in particular, propagating radicals, to unsaturated systems is potentially a reversible process (Scheme 4.46). Depropagation is cntropically favored and the extent therefore increases with increasing temperature (Figure 4.4). The temperature at which the rate of propagation and depropagalion become equal is known as the ceiling temperature (rc). Above Tc there will be net depolymerization. 

B. Radical Addition of Sulfonic Acid Derivatives to Unsaturated Systems. 189... 

Addition of P—H bonds to unsaturated systems also continues to be used as a route to heterocyclic systems. Thus base-catalysed cyclization of the phosphine (32) [prepared by the addition of methyl methacrylate (2 moles) to phenylphosphine], followed by subsequent hydrolysis and decarboxylation, affords the phosphorinanone (33). The phosphorinanone system is also directly accessible by the addition of phenylphosphine to divinyl ketones.28 The radical-initiated addition of phenylphosphine to dialkynyl systems (34) gives the heterocyclohexadienes (35).29 80 The stereochemistry of the addition of phenylphosphine to cyclo-octa-2,7-dienone to give... 

The recognition of anti-Markownikoff orientation when HBr was added to alkenes in the presence of traces of peroxides or air lead to the discovery of the large and important class of free radical addition reactions to unsaturated systems The anti-Markownikoff orientation of these reactions i.e., the preference of initial radical at-... 

Haszeldine, R. N. The addition of free radicals to unsaturated systems. IV. the direction of radical addition to hexafluoropropene. J. Chem. Soc. 3559—3564 (1953). 

Radicals add to unsaturated bonds to form new radicals, which then undergo addition to other unsaturated bonds to generate further radicals. This reaction sequence, when it occurs iteratively, ultimately leads to the production of polymers. Yet the typical radical polymerization sequence also features the essence of radical-induced multicomponent assembling reactions, assuming, of course, that the individual steps occur in a controlled manner with respect to the sequence and the number of components. The key question then becomes how does one control radical addition reactions such that they can be useful multicomponent reactions Among the possibilities are kinetics, radical polar effects, quenching of the radicals by a one-electron transfer and an efficient radical chain system based on the judicious choice of a radical mediator. This chapter presents a variety of different answers to the question. Each example supports the view that a multicomponent coupling reaction is preferable to uncontrolled radical polymerization reactions, which can decrease the overall efficiency of the process. 

Most useful reactions of perfluoroalkyl radicals involve efficient chain processes, and the challenge has been to find conditions where efficient propagation of the chain via chain transfer can occur. The development of such methodology has derived largely from the huge amount of work which has been devoted to studies of the addition of perfluoroalkyl radicals to unsaturated systems, particularly olefins. 

The calculation of rate constants for OH radical addition to >C=C< and -C=C- bonds assumes that the rate constant for OH radical addition to these carbon-carbon unsaturated bonds depends on the number, identity, and position of substituent groups around the >C=C< or -C=C- bond(s). Conjugated double bond systems are dealt with by considering the entire conjugated >C=C-C=C< system as a single unit (Atkinson, 1986), rather than as conjugated >C=C< sub-units as Ohta (1983) did. 

The radical or anion species generated by electroreduction of halides are able to add to unsaturated systems such as aromatic ring and carbonyl group. The intramolecular addition of a radical species formed by electroreduction of an aromatic iodide to an aromatic ring has been applied to the synthesis of aporphines as it is shown in the following scheme 32). 

The reaction of formamide with aromatic compounds under ultraviolet irradiation is still unexplored and only preliminary results have so far been obtained. In the cases already studied it has been found that this reaction must be sensitized with a ketonic sensitizer, usually acetone, in order to take place. The mechanism of the photoamidation of aromatic compounds certainly differs from the one of simple olefins. The detailed mechanism still awaits further experimental evidence, and in some cases involves, most probably, radical combinations and not addition of radical to unsaturated systems. Interactions of the excited sensitizer with aromatic compounds, having in some cases triplet energies similar or just a bit higher than those of the sensitizers used, must be brought into consideration. Experimentally it has been shown that the photosensitized amidation of benzene leads to benzamide (11),... 

Nikishin, G. I., and R. I. Musiafaev Free Radical Addition of N-Ethyl-acetamide to Unsaturated Systems. Dokl. Akad. Nauk SSSR 158, 1127 (1964) and references cited therein. 

Acyl radicals are very useful synthetic intermediates. Their preparation is not simple since the corresponding halides are highly electrophilic and cannot be used as radical precursors. Organocobalt compounds were proposed as suitable source of acyl radicals [44]. However, the use of acyl selenides proved to be more general [45, 46]. These radical precursors can be efficiently prepared from the corresponding carboxylic acids and esters [47]. Acyl phenyl selenides should be preferred, when possible, relative to acyl methyl selenides due to the consumption of two equivalents of tin hydride with this last system (Scheme 1) [4]. Acyl selenides have found many applications in tandem radical additions to alkenes. Examples of intermole-cular [Eq. (18)] [48,49] and intramolecular reactions [Eq. (19)] [50a] are reported. The enoyl selenide 68 give the unsaturated acyl radicals 69. This intermediate... 

The addition reactions take place at a carbon-carbon multiple bond, or carbon-hetero atom multiple bond. Because of this peculiarity, the addition reactions are not common as the first step in pyrolysis. The generation of double bonds during pyrolysis can, however, continue with addition reactions. The additions can be electrophilic, nucleophilic, involving free radicals, with a cyclic mechanism, or additions to conjugated systems such as Diels-Alder reaction. This type of reaction may explain, for example, the formation of benzene (or other aromatic hydrocarbons) following the radicalic elimination during the pyrolysis of alkanes. In these reactions, after the first step with the formation of unsaturated hydrocarbons, a Diels-Alder reaction may occur, followed by further hydrogen elimination ... 

Stereoselective addition of ribofuranosyl radicals to a, 9-unsaturated carbonyl compounds was exploited by Araki [22] in the formal synthesis of the antiobiotic Showdomycin 16 (Scheme 4). Barton [23] provided a more direct synthesis of 16 by addition of the ribofuranosyl radical, generated using the sugar telluride 17, to maleimide. Ribofuranosyl radicals also undergo addition to Tt-systems of electron-deficient aromatics such as 18, which provides a direct route to C-nucleosides [24], Addition of glycosyl radical donors to allyltributyltin was introduced by Keck... 

Thus Szwarc and co-workers (see ref. 396) have carried out extensive studies of H abstraction and addition to unsaturates of methyl radicals in iso-octane solution. Most of the work involved acetyl peroxide as the methyl radical source and subsequent experiments with azomethane confirmed the original findings. The systems yielded rate coefficients at 338°K for attack of the methyl radicals on the substrate relative to attack on iso-octane. If the rate coefficient for attack of methyl radicals on iso-octane in the gas phase was known it would be possible to make direct comparisons of gas and liquid phase reactions of methyl radicals with some substrate molecules. Unfortunately, the only available rate coefficient for methyl attack on iso-octane was measured at 773°K and it is of doubtful validity [3]. Nevertheless, the liquid phase studies of methyl radicals yield relative rate coefficients for attack on primary, secondary and tertiary C—H bonds which are fully compatible with the gas phase values. 

The OH radical is electrophilic in nature so it interacts by addition with unsaturated systems at sites of high electron density. Therefore with the nucleobases which contain a 7C-system (see Figure 1), the OH radical interacts predominantly by addition. With pyrimidines, the OH radical interacts with the C(5) =C(6) double bond to produce the radicals shown in Figure 3. These two... 

Intramolecular radical addition to isolated unsaturated bonds in the synthesis of pyrroloindoles - a ring system found in the biologically active mitosenes has been studied in detail (95TL4857), (98T2149) (Scheme 25). 

Mu-substituted free radicals had not been detected by pSR at about 100 G which had been the magnetic field intensity commonly used in the muon facilities, and the first observation was made at high transverse magnetic fields (about 3000 G) in 1978 [11, 45] and this method has sometimes been called high-field pSR . A great number of radicals have been measured since then, e.g. olefins and dienes [46], methyl-, F- and other substituted benzenes [13, 47], and triple bonds [48]. All the observed radicals are derived by Mu addition to unsaturated molecules, and thus p is automatically located at the P-position, i.e. two bond, away from the unpaired electron or delocali system. Although Mu-substituted radicals are typical entities that are created by p" " and their structures and reactivities are probed by p itself, they are not ctealt with here in detail, since they have been fully reviewed [12,49]. 

Photopolymerizable monomers and oligomers can be classified under four main groups including radical monomers and oligomers, unsaturated polyester resins, thiol-ene systems, and cationic monomers. In addition to these systems, particular photopolymerizable systems are also available such as expanding monomers, liquid crystalline monomers, and some other miscellaneous monomers. 

Radical addition to carbon-carbon unsaturated bonds has also been carried out in microflow reactors. Tributyltin hydride-mediated radical reactions of organic halides have been successfully carried out in a continuous microflow system [20]. Rapidly decomposing radical initiators such as V-65 and V-70 are fairly effective and the reactions proceed within a very short period of time. The continuous flow reaction system can be applied to gram-scale synthesis (7.6 g, 185 min) of a key intermediate for furofuran lignans (Figure 5.2). 

Most of the addition reactions observed occur by a radical mechanism. This type of reaction has been reviewed , and two chapters in this book are concerned with radical reactions of thiols. This discussion will exclude all reactions that occur via the formation of radicals. Considerably less study has been made of ionic additions of thiolates to unsaturated systems than that of radical additions. 

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