Sources of Radical Intermediates

A discussion of some of the radical sources used for mechanistic studies was given in Section 12.1.4 of Part A. Some of the reactions discussed there, particularly the use of azo compounds and peroxides as reaction initiators, are also important in synthetic chemistry. 

One of the most useful sources of free radicals in preparative chemistry is the reaction of halides with stannyl radical 

This generalized reaction sequence consumes the halide, the stannane, and the reactant X=Y and effects addition of the organic radical and a hydrogen atom to the X=Y bond. The order of reactivity of organic halides toward stannyl radicals is iodides bromides chlorides. 

The esters of A-hydroxypyridine-2-thione are another versatile source of radicals.195 The radical is formed by decarboxylation of an adduct formed by attack at sulfur by the 

SECTION 10.3. REACTIONS INVOLVING FREE-RADICAL INTERMEDIATES 

The esters of N-hydroxypyridine-2-thione have proven to be a versatile source of radicals. The radical is formed by fragmentation of an adduct resulting from attack at sulfur by the chain-carrying radical. The generalized chain sequence is as follows  

When X—Y is R3Sn—H, the net reaction is decarboxylation and reduction of the original acyloxy group. When X—Y is CI3C—Cl, the final product is a chloride. Use of CI3C—Br gives the corresponding bromide.  

There is a discussion of some of the sources of radicals for mechanistic studies in Section 11.1.4 of Part A. Some of the reactions discussed there, particularly the use of azo compounds and peroxides as initiators, are also important in synthetic chemistry. One of the most useful sources of free radicals in preparative chemistry is the reaction of halides with stannyl radicals. Stannanes undergo hydrogen abstraction reactions and the stannyl radical can then abstract halogen from the alkyl group. For example, net addition of an alkyl group to a reactive double bond can follow halogen abstraction by a stannyl radical. 

Reactions Involving Carbocations, Carbenes, and Radicals as Reactive Intermediates X) S R-C jO C°2 b CUCS N OCR II o 

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Peroxides are a common source of radical intermediates. Commonly used initiators include benzoyl peroxide, f-butyl peroxybenzoate, di-f-butyl peroxide, and r-butyl hydroperoxide. Reaction generally occurs at relatively low temperature (80° -100°C). The oxygen-oxygen bond in peroxides is weak ( 30kcal/mol) and activation energies for radical formation are low. Dialkyl peroxides decompose thermally to give two alkoxy radicals. ... 

Peroxides are a common source of radical intermediates. An advantage of the generation of radicals from peroxides is that reaction generally occurs at relatively low temperature because the bond energy of the oxygen-oxygen bond in these compounds ( 30 kcal/mol) is quite low. Several kinds of peroxide compounds have been employed. Diacyl peroxides are sources of alkyl radicals because the carboxyl radicals that are initially formed lose CO2 very rapidly ... 

Sources of Radical Intermediates Introduction of Functionality by Radical Reactions Addition Reactions of Radicals with Substituted Alkenes Cyclization of Free-Radical Intermediates Fragmentation and Rearrangement Reactions... 

Peroxides are a common source of radical intermediates. An advantage of the generation of radicals from peroxides is that reaction generally occurs at relatively... 

A more practical, atom-economic and environmentally benign aziridination protocol is the use of chloramine-T or bromamine-T as nitrene source, which leads to NaCl or NaBr as the sole reaction by-product. In 2001, Gross reported an iron corrole catalyzed aziridination of styrenes with chloramine-T [83]. With iron corrole as catalyst, the aziridination can be performed rmder air atmosphere conditions, affording aziridines in moderate product yields (48-60%). In 2004, Zhang described an aziridination with bromamine-T as nitrene source and [Fe(TTP)Cl] as catalyst [84]. This catalytic system is effective for a variety of alkenes, including aromatic, aliphatic, cyclic, and acyclic alkenes, as well as cx,p-unsaturated esters (Scheme 28). Moderate to low stereoselectivities for 1,2-disubstituted alkenes were observed indicating the involvement of radical intermediate. 

Scheme 10.17 illustrates allylation by reaction of radical intermediates with allyl stannanes. The first entry uses a carbohydrate-derived xanthate as the radical source. The addition in this case is highly stereoselective because the shape of the bicyclic ring system provides a steric bias. In Entry 2, a primary phenylthiocar-bonate ester is used as the radical source. In Entry 3, the allyl group is introduced at a rather congested carbon. The reaction is completely stereoselective, presumably because of steric features of the tricyclic system. In Entry 4, a primary selenide serves as the radical source. Entry 5 involves a tandem alkylation-allylation with triethylboron generating the ethyl radical that initiates the reaction. This reaction was done in the presence of a Lewis acid, but lanthanide salts also give good results. 

The radical source must have some functional group X that can be abstracted by trialkylstannyl radicals. In addition to halides, both thiono esters and selenides are reactive. Allyl tris(trimethylsilyl)silane can also react similarly.232 Scheme 10.11 illustrates allylation by reaction of radical intermediates with allylstannanes. 

The photoinduced initiation reaction may have the disadvantage of poor quantum yields, arising from a fast backward ET which annihilates the ion pair before its cage separation. This means a poorly efficient source of radicals. However, if the photochemical ET is the initiation of a very efficient radical chain process, a poor quantum yield in the reaction may turn to an advantage because small extent of production of the intermediates (Ar, ArX- , ArNu ) will disfavour the proposed termination steps of the mechanism. 

Thus, it has been proposed that the homolytic decomposition of hydroperoxides can be induced by sulfenic acid (12,13). There is evidence that various carboxylic acids can promote radical formation from hydroperoxides at elevated temperatures (II, 14). The intermediate thiosul-furous acid (Reaction 7) itself may function as the source of radicals, since sulfinic acid is known to initiate the radical polymerization of vinyl monomers at 20°C (15). Based on the AIBN-initiated oxidation of cumene, Koelewijn and Berger (16) proposed that pro-oxidant effects arise from catalysis of the radical decomposition of hydroperoxides by intermediate compound formation between the hydroperoxide and sulfoxide. However, under our conditions hydroperoxide was stable in the presence of sulfoxide alone. 

The formation of the intermediate carbocation is convincingly proved by the transformation of 1,1-dimethylcyclohexadiene into o-xylene in the presence of peroxide (the source of radicals) and copper ions... 

We may draw a distinction in basic mechanism of formation of polymers and this is indicated schematically in Figure 5. For functionalised monomers e.g. an alkene it is possible under certain conditions to produce linear polymers. These arise from conventional cationic or radical addition mechanism the plasma then acting as a source of reactive intermediates to initiate the 2 plasma. This is termed plasma induced polymerizations (PIP). 

The chemical pathways leading to acid generation for both direct irradiation and photosensitization (both electron transfer and triplet mechanisms) are complex and at present not fully characterized. Radicals, cations, and radical cations aH have been proposed as reactive intermediates, with the latter two species beHeved to be sources of the photogenerated acid (Fig. 20) (53). In the case of electron-transfer photosensitization, aromatic radical cations (generated from the photosensitizer) are beHeved to be a proton source as weU (54). 

New radicals come exclusively from the decomposition of the intermediate hydroperoxide (eq. 4), provided no other radical sources, eg, peroxidic impurities, are present. Hydroperoxides have varying degrees of stabiUty, depending on their stmcture. They decompose by a variety of mechanisms and are not necessarily efficient generators of new radicals via thermolysis (19,20). 

Reaction 21 is the decarbonylation of the intermediate acyl radical and is especially important at higher temperatures it is the source of much of the carbon monoxide produced in hydrocarbon oxidations. Reaction 22 is a bimolecular radical reaction analogous to reaction 13. In this case, acyloxy radicals are generated they are unstable and decarboxylate readily, providing much of the carbon dioxide produced in hydrocarbon oxidations. An in-depth article on aldehyde oxidation has been pubHshed (43). 

In order for the cyclooxygenase to function, a source of hydroperoxide (R—O—O—H) appears to be required. The hydroperoxide oxidizes a heme prosthetic group at the peroxidase active site of PGH synthase. This in turn leads to the oxidation of a tyrosine residue producing a tyrosine radical which is apparendy involved in the abstraction of the 13-pro-(5)-hydrogen of AA (25). The cyclooxygenase is inactivated during catalysis by the nonproductive breakdown of an active enzyme intermediate. This suicide inactivation occurs, on average, every 1400 catalytic turnovers. 

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