Radical chain sequence

This comparison suggests that of these two similar reactions, only alkene additions are likely to be a part of an efficient radical chain sequence. Radical additions to carbon-carbon double bonds can be further enhanced by radical stabilizing groups. Addition to a carbonyl group, in contrast, is endothermic. In fact, the reverse fragmentation reaction is commonly observed (see Section 10.3.6) A comparison can also be made between abstraction of hydrogen from carbon as opposed to oxygen. 

The mechanism operating in these reactions seems to follow a radical path that could be related to the classic Haber-Weiss radical-chain sequence [32] based on the couple [Rh2 H jt-OAc)4]/[Rh2 (p.-OAc)4j. 

A related radical addition/5-exo cyclization cascade involving addition of sulfonyl radicals to alkynes has been used for the diastereoselective synthesis of bicyclic p-lactams 182 from the p-lactamic enyne precursor 181 (Scheme 2.33). In this radical chain sequence, where tosyl bromide is used as source of sulfonyl radicals, the final product is a mixture of epimers (90 10) at the newly formed exocyclic chiral center. 

Citation of the classic chain reaction for lipid oxidation persists even though, as product analysis and studies of mechanisms have become more sophisticated, there is now considerable evidence that only Reactions 1, 2, and 5 (and perhaps also 6) of Figure 1 are always present. Research has shown that, although hydrogen abstraction ultimately occurs, it is not always the major fate of the initial peroxyl or alkoxyl radicals. Indeed, lipid alcohols from H abstraction are relatively minor products of lipid oxidation. There are many competing alternative reactions for LOO and LO that propagate the radical chain but lead to different kinetics and different products than expected from the classic reaction sequence (5, 6, 21). A more detailed consideration of each stage shows how this basic radical chain sequence portrays only a small part of the lipid oxidation process and products, and a new overall reaction scheme for lipid oxidation is needed. 

Current information raises questions about the literal application of the classic free radical chain sequence to lipid oxidation. Observed products do not match those predicted Many studies have now shown that hydroperoxides are not exclusive products in early stages and lipid alcohols are not even major products after hydroperoxide decomposition. Product distributions are consistent with multiple pathways that compete with each other and change dominance with reaction conditions and system composition. Rate constants show no strong preference for H abstraction, cyclization, addition, or scission, which partially explains the mixmre of products usually observed with oxidizing lipids. It could be argued that the reactions in Figure 1 accurately describe early processes of lipid oxidation, but LOO rate constants considerably higher for cyclization than for abstraction contradict this. 

The predominant reaction for the formation of cyclohexanol and cyclohexanone is the Russell mechanism of decomposition of secondary cyclohexylperoxy radicals, vhich first yields the product of coupling and then reacts by a non-radical, six-center 1,5-H-atom shift (termination of the radical-chain sequence) ... 

Specific to allylstannanes is a radical-chain sequence (Scheme 81). ... 

Allylstannanes are made by very similar methods to those used for allylsilanes, where the same problems arise when unsymmetrical allyl nucleophiles are treated with tin halides.24,110 To solve this problem, there are tin equivalents of the reactions in Schemes 63, 65,110,140 69,141 70,142 75143 and 77.144 Specific to allylstannanes is a radical-chain sequence (Scheme 81 ).88... 

The replacement of a carboxylic acid group by nitrile functionality can also be used for the preparation of labeled compounds, and conditions for alkaline hydrolysis which did not lead to conjugation in skipped dienes like linoleic acid were developed by the Barton group. In this case, the free-radical chain sequence is straightforward, with the methanesulfonyl (or p-toluenesulfonyl) radical acting as the chain carrier [26], This methodology also represents an interesting way for the preparation of nitriles without the necessity for amide formation followed by dehydration. 

If one of the reactions in a radical chain sequence is too slow to compete effectively with radical-radical reactions, the chain will collapse. Slow reactions of simple silanes such as Et3SiH with alkyl radicals precludes their use in the tin hydride method. Although quite reactive with alkyl radicals, thiols and selenols fail in the tin hydride method because the thiyl and selenyl radicals do not react rapidly with organic halide precursors. Nonetheless, it is possible to use thiols and selenols in tin hydride sequences when a Group 14 hydride is used as a sacrificial reducing agent. The thiyl or selenyl radical reacts with the silane or stannane rapidly, and the silicon- or tin-centered radical thus formed reacts rapidly with the organic halide [8], In practice, benzeneselenol in catalytic amounts has been used in radical clock studies where BusSnH served as the sacrificial reductant [9]. 

For transformations based on stannane-mediated radical chain sequences, selenol esters are the precursors of choice owing to their ease of preparation, stabilities, and ability to accomplish Sh2 reactions (see Sect. 3.2.1). However, replacing the selenol esters by thiol esters in these tributyltin hydride- or allyl-tributylstannane-mediated chain reactions would be attractive from a synthetic viewpoint. 

Generation of Acyl Radicals. The generation of acyl radicals from simple thiol esters, either by photochemical methods or in conjunction with silanes and stannanes, is complicated by low quantum yields and lack of reactivity. This problem was circumvented by the inclusion of an additional propagation step, an intramolecular homolytic substitution (Sh2) of an aryl radical on the sulfur atom of a thiol ester carbonyl group (eq 2), in a radical chain sequence. 

The i-butoxy radical itself can abstract a-hydrogens directly. This is evident from studies with di-i-butyl peroxide, which decomposes homolytically at temperatures above 125°c ((i-Bu)2022 i-BuO ), Primary and secondary alkylamines react to form imines . The mechanism has been viewed as a radical chain sequence following abstraction of the a-hydrogen (Scheme 35). Tertiary alkylamines... 

Chlorine atoms, in turn, react efficiently with ozone in a radical chain sequence. 

The mechanism of the addition reaction under these conditions is not an ionic sequence rather, it is a much faster radical chain sequence. The reason is that the activation energies of the component steps of radical reactions are very small, as we observed earlier during the discussion of the radical halogenation of alkanes (Section 3-4). Consequently, in the presence of radicals, anti-Markovnikov hydrobromination simply outpaces the regular addition pathway. The initiation steps are... 

A thermal acylation via a radical chain sequence was achieved for chloranil (38) and benzaldehyde (similar to Scheme 11) at elevated temperatures using benzoyl peroxide as a radical initiator. As an example, the monoester 39 was readily obtained in yields of 75 to 80% at 120°C. Thus, Schenck concluded that a free radical chain mechanism during photolysis should occur solely at higher temperatures. ° ... 

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