5-hexenyl radical, cyclization

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

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.

In contrast to the large body of kinetic data that is available on hexenyl radical cyclizations, relatively little is known about the cyclizations of azahexenyl analogs. Only very recently have the detailed studies of Newcomb permitted a complete analysis of a useful parent cyclization.173 As illustrated in equation (6), aminyl radical (55) cyclizes to (56) with a rate constant of about 3 x 103 s 1, but (56) reverts to (55) with a slightly greater rate constant of 7 x 103 s 1. That the cyclization of (55) is very slow, and that (55) is actually slightly preferred at equilibrium over (56), can be understood in terms of the above explanations for N—H bond strengths. 

The overall reactivities of these radicals in their ummolecular 5-hexenyl cyclization processes reflects those same factors which affect the reactivity of partially-fluorinated radicals in their bimolecular addition reactions with alkenes, such as styrene. Table 17 indicates this clearly, and it also reflects the general leveling effect which would be expected for the more facile unimolecular cyclization processes which have log A s about 1-2 units larger than those for the bimolecular additions. 

The observation that formation of five-membered rings is favored is consistent with the findings of Beckwith125 the 5-hexenyl radical undergoes cyclization to the cyclopentylmethyl radical 75 times faster than to the cyclohexyl radical. 

The first proposal of intramolecular addition of 5-hexenyl radicals was independently reported in 1957 by Marvel and by Butler. They polymerized 1,6-dienes and, finding that the products were devoid of unsaturation, assumed that the initially produced radicals had cyclized their work will be discussed in a later section. Also to be discussed is the pioneering work of Friedlander who, in 1958, reported the cyclization of diallyl ethers and diallyl thioethers under free radical conditions. 

This certainly very incomplete and fast growing list of examples was provided in order to show that the 5-hexenyl radical tool may be used in many cases. Other examples in which the 5-hexenyl cyclization also affords kinetic values will be described in Section XII.2. 

These warnings should not lead to the conclusion that the free radical cyclization (or ring-opening) tool must be avoided. Quite the contrary, the 5-hexenyl cyclization is certainly one of the best probes for the presence of alkyl free radical intermediates, but in dubious cases, as for instance those involving organometallic compounds, other probes are needed. 

The reactivity order of alkylhalides that is tertiary > secondary > primary suggests the reaction does not proceed via mechanism but via radical or car-bocation like mechanism. To discriminate between the two mechanisms 1,1-dimethyl-5-hexenyl chloride is reacted with tributyltin hydride (which involves radicals) and with the lithium di-n-butyl-9-BBN ate complex. It is well known that 5-hexenyl radicals undergo cyclization to give cyclopentylmethyl radicals [31], whereas hexenyl cation cyclizes to cyclohexyl cation [32]. As reduction with ate complex (Chart 25.13) affords none of the cyclopentyl derivatives, thus rules out the radical mechanism. 

Pig. 9 Different radical cyclizations investigated in ref. 95 1 cyclization of hexenyl radicals, II cyclization of acyl-substituted hexenyl radicals and III cascade radical reactions. (Reproduced with permission from /. Org. Chem., 2007, 72, 348. Copyright 2007 American Chemical Society). 

The 5-hexenyl cyclization is clearly xmder kinetic rather than under thermodynamic control since the thermodynamically favoured product would be the cyclohexyl radical. It has been suggested that the 5- rather than the 6-membered ring is produced because bond formation requires the approach of the radical within the plane of the 7r-orbital and along an axis extending above one of the terminal atoms of the double bond either approximately vertically (, , or at an angle of about 109° to the double... 

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. 

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]. 

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 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) ... 

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