Radicals carbon centered

In this section vc consider the properties and reactions of three classes of carbon-centered radicals alkyl radicals (3.4.1.1), aryl radicals (3.4.1.2) and acyl radicals (3.4.1.3). 

Primary radical termination involving alkyl radicals is described in Sections 

5 and 7.4.3. Their reactions with monomers are also discussed in Sections 2.3 (fundamental aspects) and 4.5.4 (model propagation radicals). Their chemistry has been reviewed by Fischer and Radom, Tedder,Beckwith,  

Alkyl radicals, when considered in relation to heteroatom-centered radicals (e.g. r-butoxy, benzoyloxy), show a high degree of chemo- and regiospecificity In their reactions. A discussion of the factors intluencing the rate and regiospecificity of addition appears in Section 2,3. Significant amounts of head addition arc observed only when addition to the tail-position is sterically inhibited as it is in a,p-disubstituted monomers. For example, with p-alkylacrylates, cyclohexyl 

Rate constants for reactions of carbon-centered radicals for the period through 1982 have been compiled by Lorand and Asmus and Bonifacic and for 1982-1992 by Roduner and Crocket The recent review of Fischer and Radom should also be consulted/ Absolute rate constants for reaction with most monomers lie in the range 10 -10 M s. Rate data for reaction of representative primary, secondary, and tertiary alkyl radicals with various monomers are summarized in Table 3,6. 

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Formation of carbon centered radicals tin hydride reduction of... 

Carbon-centered radicals generally react very rapidly with oxygen to generate peroxy radicals (eq. 2). The peroxy radicals can abstract hydrogen from a hydrocarbon molecule to yield a hydroperoxide and a new radical (eq. 3). This new radical can participate in reaction 2 and continue the chain. Reactions 2 and 3 are the propagation steps. Except under oxygen starved conditions, reaction 3 is rate limiting. 

Cycloalkoxy radical intermediates are readily generated from a parent alcohol by various methods (e.g., nitrite ester photolysis, hypohalite thermolysis, lead tetraacetate oxidation) (83MI1). Once formed, reactive cycloalkoxy radicals undergo /3-scission to produce a carbonyl compound and a new carbon-centered radical. 

Vinyl radical formation by intramolecular addition of a carbon-centered radical to an alkyne... 

The success of intramolecular conjugate additions of carbon-centered radicals in multifunctional contexts is noteworthy. Compound 57 (see Scheme 10), prepared by an interesting sequence starting from meto-toluic acid (54) (see 54 > 55 > 56 > 57), can be converted to the highly functionalized perhydroindane 58 through an intramolecular conjugate addition of a hindered secondary radical.21-22 This radical cyclization actually furnishes a 6 1 mixture of perhydroindane diastereoisomers, epimeric at C-7, in favor of 58 (96 % total yield). It should be noted that a substantially less strained cis-fused bicyclo[4.3.0] substructure is formed in this cyclization. 

In contrast to carbanions, carbon-centered radicals tolerate oxygenated functionality in the -position... 

Trialkyltin groups p to a carbon-centered radical are readily eliminated... 

The wide variety of methods available for the synthesis of orga-noselenides,36 and the observation that the carbon-selenium bond can be easily cleaved homolytically to give a carbon-centered radical creates interesting possibilities in organic synthesis. For example, Burke and coworkers have shown that phenylselenolactone 86 (see Scheme 16), produced by phenylselenolactonization of y,S-unsaturated acid 85, can be converted to free radical intermediate 87 with triphenyltin hydride. In the presence of excess methyl acrylate, 87 is trapped stereoselectively, affording compound 88 in 70% yield 37 it is noteworthy that the intramolecular carbon-carbon bond forming event takes place on the less hindered convex face of bicyclic radical 87. 

Carbon-centered radicals generated by Barton s thiohydroxamate method can also participate in ring-forming reactions (see Scheme 26).52b,s3 For example, irradiation of 129 results in the formation of compound 130 (82% yield). The outcome of this transformation is reminiscent of Stork s elegant radical cyclization/trapping processes (see Schemes 7 and 8), in that/botn alkene carbon atoms have become functionalized. / I... 

Carbon-centered radicals have been shown to undergo addition reactions with azirine-3-carboxylates. Methyl 2-(2,6-dichlorophenyl)azirine-2-carboxylate thus reacts with alkyl and aryl iodides in the presence of triethylborane to give aziridines in good yields. The radical approaches from the opposite face to the aryl substituent, giving the cis products as single diastereoisomers (Scheme 4.43) [63],... 

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

The Arrhenius frequency factors [log(T/M V)] for addition of carbon centered radicals to the unsubstiUited terminus of monosubslituted or 1,1-disubstituted olefins cover a limited range (6.0-9.0), depend primarily on the steric demand of the attacking radical and are generally unaffected by remote alkene substituents. Typical values of log(T/M" V) are ca 6.5 for tertiary polymeric (e.g. PMMA ), ca 7.0 for secondary polymeric (PS, PMA, and ca 7.5, 8.0 and 8.5 for small tertiary (e.g. /-C4H9 ), secondary (i-CiH ) and primary (CHj, CbHs ) radicals respectively (Section 4.5.4).4 For 1,2,2-trisubstituted alkenes the frequency factors arc about an order of magnitude lower.4 The trend in values is consistent with expectation based on Iheoretical calculations. 

The hydrogen abstraction addition ratio is generally greater in reactions of heteroatom-centered radicals than it is with carbon-centered radicals. One factor is the relative strengths of the bonds being formed and broken in the two reactions (Table 1.6). The difference in exothermicity (A) between abstraction and addition reactions is much greater for heteroatom-centered radicals than it is for carbon-centered radicals. For example, for an alkoxy as opposed to an alkyl radical, abstraction is favored over addition by ca 30 kJ mol"1. The extent to which this is reflected in the rates of addition and abstraction will, however, depend on the particular substrate and the other influences discussed above. 

The last comprehensive review of reactions between carbon-centered radicals appeared in 1973.142 Rate constants for radical-radical reactions in the liquid phase have been tabulated by Griller.14 The area has also been reviewed by Alfassi114 and Moad and Solomon.145 Radical-radical reactions arc, in general, very exothermic and activation barriers are extremely small even for highly resonance-stabilized radicals. As a consequence, reaction rate constants often approach the diffusion-controlled limit (typically -109 M 1 s"1). 

The latter pathway is rare for reactions involving only carbon-centered radicals and will not be considered further in this chapter. 

The combination of carbon-centered radicals usually involves head-to-head (a,a ) coupling. Exceptions to this general rule occur where the free spin can be delocalized into a n-system. The classic example involves the triphenylmethyl radical (13) which combines to give exclusively the a-para coupling product (26), Scheme I.8).27 This chemistry is also seen in cross reactions of 13 with other tertiary radicals.146... 

Reactions between carbon-centered radicals generally give a mixture of disproportionation and combination. Much effort has been put into establishing the relative importance of these processes. The ratio of disproportionation to combination (kt /k]t ) is dependent on the structural features of the radicals involved and generally shows only minor variation with solvent, pressure, temperature, etc. 

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