Hexenyl radical

Effects of substituent on the regiochemistry of the 5-hexenyl radical cyclization... 

Cyclizations involving iodine-atom transfers have been developed. Among the most effective examples are reactions involving the cyclization of 6-iodohexene derivatives. The 6-hexenyl radical generated by iodine-atom abstraction rapidly cyclizes to a cyclo-pentylmethyl radical. The chain is propagated by iodine-atom transfer. 

Other transformations of the radicals are also possible. For example, the 5-hexenyl radical partially cyclizes in competition with coupling ... 

The use of radical cyclizations to make five-membered rings has become a very important tool for synthetic chemists Although there has been a virtual explosion of reports in the literature regarding the cyclization of 5-hexenyl radicals to cyclopentyl carbinyl radicals in all types of hydrocarbon systems [55], the use of this cyclization for the synthesis of fluorme-containing cyclopentanes has been largely ignored... 

The first example of a cyclization of fluorine-containing 5-hexenyl radicals was the study of the radical-iniOated cyclodimenzation reaction of 3,3,4,4-tetra-fluoro-4-iodo-1-butene. In this reaction, the intermediate free radical adds either to more of the butene or to an added unsaturated species [54, 55] (equation 56). Electron-deficient alkenes are not as effective trapping agents as electron-nch alkenes and alkynes [55]. 

It was established in the early 1960s that hexenyl radicals and simple derivatives gave 1,5- rather than 1,6-ring closure under conditions of kinetic... 

Giese and Kretzschmar7j found the rate of addition of hexenyl radicals to methyl acrylate increased 2-fold between aqueous tetrahydrofuran and aqueous ethanol, Salikhov and Fischer74 reported that the rate constant for /-butyl radical addition to acrylonitrile increased 3.6-fold between tetradecane and acetonitrile. Bednarek et al75 found that the relative reactivity of S vs MMA towards phenyl radicals was ca 20% greater in ketone solvents than it was in aromatic solvents. 

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... 

The understanding of the mechanism of cyclopolymerization has been one of the initial driving forces responsible for studies on the factors controlling the mode of ring closure of 5-hexenyl radicals and other simple model compounds.113... 

The preferential 1,5-ring closure of unsubsliluted 5-hexenyl radicals has been attributed to various factors these arc discussed in greater detail in Section 2.3.4. The mode and rate of cyclization is strongly influenced by substituents. The results may be summarized as follows (Scheme 4.13) ... 

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

Activation parameters. Calculate AW and AS for the cyclization of the 5-hexenyl radical, whose rate is given in Eq. (5-39). 

Competition kinetics. Cyclization of the 1-hexenyl radical competes with the reaction with BihSnH to form methylcyclopentane. 

Eisch, Behrooz and Galle196 give compelling evidence for the intervention of radical species in the desulphonylation of certain acetylenic or aryl sulphones with metal alkyls having a lower oxidation potential at the anionic carbon. The primary evidence presented by these workers is that the reaction of 5-hexenylmagnesium chloride outlined in equation (85) gives a mixture of desulphonylation products, in accord with the known behaviour of the 5-hexenyl radical, in which the cyclopentylmethyl radical is also formed. 

Based on a unimolecular cyclization rate constant of 5 x 105s" 1 for A5-hexenyl radical at 318 K (cf. Reference 34). 

A5-hexenyl substituent, extensive cyclization occurs to yield the cyclopentylcarbinyl product from the yields of uncyclized and cyclized products for A5-hexenylmercury chloride, the rate constants for equation 50 have been estimated (vide supra). The SH2 reaction 49 has also been invoked to be the key step in the alkylation of -substituted styrenes by a free-radical addition-elimination sequence, namely96... 

One experimental test for the involvement of radical intermediates is to study 5-hexenyl systems and look for the characteristic cyclization to cyclopentane derivatives (see Part A, Section 11.2.3). When 5-hexenyl bromide or iodide reacts with LiAlH4, no cyclization products are observed. However, the more hindered 2,2-dimethyl-5-hexenyl iodide gives mainly cyclic product.164... 

One of the fundamental questions about the mechanism is whether the radical is really free in the sense of diffusing from the metal surface.7 For alkyl halides, there is considerable evidence that the radicals behave similarly to alkyl free radicals.8 One test for the involvement of radical intermediates is to determine whether cyclization occurs in the 6-hexenyl system, where radical cyclization is rapid (see Part A, Section 12.2.2). 

Small amounts of cyclized products are obtained after the preparation of Grignard reagents from 5-hexenyl bromide.9 This indicates that cyclization of the intermediate radical competes to a small extent with combination of the radical with the metal. Quantitative kinetic models that compare competing processes are consistent with diffusion of the radicals from the surface.10 Alkyl radicals can be trapped with high efficiency by the nitroxide radical TMPO.11 Nevertheless, there remains disagreement about the extent to which the radicals diffuse away from the metal surface.12... 

Another major influence on the direction of cyclization is the presence of substituents. Attack at a less hindered position is favored by both steric effects and the stabilizing effect that most substituents have on a radical center. These have been examined by DFT (UB3LYP/6-31+G ) calculations, and the results for 5-hexenyl radicals are shown in Figure 10.14. For the unsubstituted system, the 5-exo chair TS is favored over the 6-endo chair by 2.7kcal/mol. A 5-methyl substituent disfavors the 5-exo relative to the 6-endo mode by 0.7kcal/mol, whereas a 6-methyl substituent increases the preference for the 5-exo TS to 3.3 kcal/mol.322... 

Fig. 10.13. MM2 models of exo and endo cyclization transition structures for 5-hexenyl, 6-heptenyl, and 7-octenyl radicals. Reproduced from Tetrahedron, 41, 3925 (1985), by permission of Elsevier.

Rearrangement of trivalent (5-hexenyl)Co(salen) proceeds via a radical chain process leading to the isomeric cyclopentylmethyl complex.1387 The efficiency with which this rearrangement occurs is dependent on the presence of trace impurities or 02. The selective reaction of alcohols (ROH) with arylglyoxals (ArCOCHO) to give a-aryl-a-hydroxyacetic esters ArCH(0H)C02R is catalyzed by compounds of this family.1388... 

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... 

Since kc is known with reasonable precision, A T can be determined. The procedure was employed to estimate kT using several different traps. The temperature range for these experiments was limited by experimental constraints but activation energies for trapping 5-hexenyl radicals by MNP and PBN were estimated to be ca. 2.0 and 3.2 kcal mol-1 respectively, within rather large error limits log A for each trap is ca. 8. 

Table II. Most of the data was obtained from radical clock studies. The neophyl radical rearrangement24 [Eq. (2)] was used for the majority of the kinetic data in Table II, but the ring expansion rearrangement reactions25-27 of radicals 7 and 8, cyclizations of 5-hexenyl type radicals,...

The kinetic data for these reactions are numerous, as shown in Table VI. Most of values were obtained by radical clock methods. The ring expansion of radical 7 has been employed as the clock in a study that provided much of the data in Table VI.74 Cyclizations of 5-hexenyl-type radicals also have been used as clocks,75-77 and other competition reactions have been used.78 Hydrogen atom abstraction from n-Bu3GeH by primary alkyl radicals containing a trimethylsilyl group in the a-, >8-, or y-position were obtained by the indirect method in competition with alkyl radical recombi-... 

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