Hexenyl radical rearrangements

Cyclizations of carbon radicals forming 6-membered rings during polymerizations were reported in 1957 (equation 75) and Julia and his co-workers began systematic studies of these reactions in 1960.  

The reaction (equation 76) of the hexenyl radical 47 forming cyclopentyl-methyl radical was discovered independently in several laboratories and has been of pervasive utility in both synthetic and mechanistic studyThe competition between formation of cyclopentylcarbinyl and cyclohexyl radicals favors the former even though the latter is more stable, and this kinetic preference is explained by more favourable transition state interaction. The effects of substituents on the double bond, heteroatoms in the chain, and many other factors on the partitioning between these two paths have been examined. In the gas phase above 300°C, methylcyclopentane has been observed to form cyclohexane via isomerization of cyclopentylmethyl radicals into the more stable cyclohexyl radicals.  

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Other radicals undergo rearrangement in competition with bimolecular processes. An example is the 5-hexenyl radical (5). The 6-heptenoyloxy radical (4) undergoes sequential fragmentation and cyclization (Scheme 3.8).1S... 

A better-known example of a free radical clock is the 5-hexenyl radical. Timing is provided by the rearrangement reaction... 

A more recent example is found in the work of Schmid and Ingold (1978), who used the rate of rearrangement (17) of 5-hexenyl radicals into cyclopentylmethyl radicals (R- and R - in Scheme 5) to time the spin trapping of primary alkyl radicals. In this system, both R and R are primary alkyl, and their spin adducts with several traps therefore have virtually indistinguishable spectra. This difficulty was circumvented by labelling C-l in the hex-5-enyl radical with 13C the unrearranged radical then gives spin... 

The kinetic data for the reaction of primary alkyl radicals (RCH2 ) with a variety of silanes are numerous and were obtained by applying the free-radical clock methodology. The term free-radical clock or timing device is used to describe a unimolecular radical reaction in a competitive study [2-4]. Three types of unimolecular reactions are used as clocks for the determination of rate constants for this class of reactions. The neophyl radical rearrangement (Reaction 3.1) has been used for the majority of the kinetic data, but the ring expansion rearrangement (Reaction 3.2) and the cyclization of 5-hexenyl radical (Reaction 3.3) have also been employed. 

As with any intermediate, a transient radical can be implicated from products formed in a reaction specific to the radical of interest. Experimentally, this is the basis of so-called mechanistic probe studies. An application of this method might employ, for example, 6-bromo-l-hexene as a probe for a radical intermediate as shown in Figure 4.3. If the 5-hexenyl radical is formed as a transient with an adequate lifetime, then cyclization of this radical to the cyclopentyhnethyl radical could eventually give the cyclic product, and detection of the cyclic product provides evidence that a radical was formed. The mechanistic probe approach is deceptively simple, however. To be useful, one must exclude other possibilities for formation of the rearranged product and demonstrate that the transient was formed in the reaction of interest and not in a side reaction. The latter is especially difficult to demonstrate, and, unfortunately, some mechanistic probe studies that seemingly provided proof of radical intermediates were later found to be complicated by radical-forming side reactions. 

Figure 4.3. Design of a radical probe mechanistic study. Formation of the rearranged product implicates the intermediate 5-hexenyl radical that cyclized to cyclopentylmethyl.

Although radicals are not nearly so prone to rearrangement as are, for example, carbocations, there are a few such rearrangements which have become identified as characteristic of carbon radicals. These include radical cyclizations, particularly the 5-hexenyl radical cyclization, and radical C-C bond cleavages, particularly the cyclopropylcarbinyl to allyl carbinyl radical rearrangement. In hydrocarbon systems, as organic synthetic chemists have learned how to control rapid chain processes, such rearrangements have become important synthetic tools [176-179]. 

Radical rearrangement products from, for example, 6-hexenyl iodide and vinyl iodide are minimal, although the cyclopropylcarbinyl example (Scheme 49) shows the nearly complete rearrangement typical of a cyclopropylcarbinyl radical. 

Radical clock rearrangements can be used to provide evidence for radical intermediates these include the ring opening of cyclopropylmethyl radical and the ring closing of the hexenyl radical (equation 21). 

Sigmatropic rearrangement of deuterium-labeled bicyclo[3.1.0]hexenyl radicals occur below — 60°C (equation 31) and are faster than ring-opening Lifetimes for ringopening of some cyclopropyl-substituted radical anions (156) have been studied, as well as the ESR spectra of p-cyclopropylnitrobenzene radical anion (157). ... 

The 5-hexenyl radical 131 rearranges in a highly regiospecific manner to give mainly the cyclopentylcarbinyl radical 132. The cyclohexyl radical 133 is formed only as a side product89). 

An excellent measure of radical involvement for certain types of studies relies upon the rearrangement rates of organic radicals that might be formed under the reaction conditions. Thus, if a free 5-hexenyl radical is formed in the oxidative addition of 5-hexenyl bromide, the product will contain a cyclopentylmethyl group. The rearrangement of the radical occurs at a rate of 10 s so that if the radical has a lifetime of more than about lO " s, it will rearrange. This technique for the demonstration of radical paths has been used in a number of cases... 

The first question is if no cyclization to the (Cy5) compounds is observed when the 5-hexenyl radical is chosen, is it possible to rule out the formation of an alkyl radical R on the reaction pathway The answer is no, not if fast competitive intermolecular reactions are expected. In this case, it is necessary to work at low concentrations in order to favor the intramolecular process but even under these conditions, very low yields of cyclized products are sometimes obtained. The use of the faster ring-opening processes (see Section XII. 1.D) will be then a useful complementary probe. But there is a case where even these faster reactions cannot afford a positive answer, when the radical intermediate reacts, by dimerization or disproportionation, with another radical in the solvent cage, since these processes are faster than the rearrangement processes. 

Knowledge of the cyclization rate of the 5-hexenyl radical has also been used to study cage reactions of alkyl radicals generated in solution from diacyl peroxides or to distinguish between intra- and intermolecular pathways in the Wittig rearrangement. It has also been used to study the mechanism of the deshalogenation of 1,4-, 1,5-, and 2,3-dihaloalkanes by alkali... 

In many cases, particularly for the study of fast reactions (ky> key in Scheme 164), the opening of the cyclopropylmethyl radical to the isomeric allyl-carbinyl radical, one thousand times faster than the cyclization of the 5-hexenyl radical, is a useful complementary tool. It has been used mainly by Kochi for the study of cage reactions of alkyl radicals in solution as well for the study of ligand and electron transfer oxidations of alkyl radicals. Furthermore, in the last three studies the knowledge of the fate of the isomeric cyclobutyl intermediate was very useful in distinguishing between a homolytic (no rearrangement of the cyclobutyl radical) and a heterolytic pathway (fast... 

One of the most useful free radical rearrangements is the ring closure of the 5-hexenyl radical to form cyclopentylcarbinyl rather than cyclohexyl radical. Use group increments to estimate the relative energies of the 5-hexenyl, cyclopentylcarbinyl, and cyclohexyl radicals. 

Radical clocks are one experimental technique that has received considerable use in the analysis of radical reactions. Most radical clocks involve an intramolecular free radical rearrangement that proceeds with a well-defined rate constant. The prototype is the rearrangement of 5-hexenyl radical to cyclopentylmethyl radical, which occurs with a unimo-lecular rate constant of 1.0 X 10 s" at 25 °C (Eq. 8.75). The clock strategy is to embed a 5-hexenyl unit into the reactive system of interest. If a radical forms, and if its lifetime is comparable to or greater than 10 s, cyclopentylmethyl-derived products should form. 

Another strong indication that contributes to show the intermediacy of R radicals consists in testing the reaction with 1-hexenyl bromide as a RX substrate. It is indeed known that the 1-hexenyl radical very rapidly rearranges to give the... 

In the foregoing we have seen how kinetic E.S.R. spectroscopy has been used to solve a long-standing problem in reaction mechanism. I now want to turn to a different radical rearrangement reaction, the cyclization of the 5-hexenyl radical, JU, to the cyclopentylmethyl radical, TR ... 

These various rearranged dimers corresponded to approximately 65 percent of the product. The hydrazine, the product of the N-N-coupling of the first formed radical, was isolated in less than one percent yields. Thus, in the hexenyl radical case the cyclization does not compete well with rearrangement. 

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