Radical olefin cyclization

Pentacyclosqualene, the symmetrical hydropicene corresponding to squalene, has not been made by acid-induced cation-olefin cyclization of squalene, despite considerable experimental study. A simple, convergent synthesis of pentacyclosqualene using cation-olefin cyclization to generate ring C was developed. The Cjo-framework was constructed by radical coupling to a tetracyclic intermediate that was also used for the synthesis of onoceradiene. 

The major product of the keto olefin cyclizations often corresponds to what one would predict, assuming the intermediate ketyl behaves like the corresponding monoradical (Eq. 34). For example, given an option between a 5-exo and a 6-endo-trig cyclization, the former predominates in radical cyclizations [51], and constitutes the exclusive cyclization path in the electrochemical counterpart, 110 - 112 [47]. In addition, the stereochemical outcome parallels that of the radical... 

Recently it has been shown that radical anionic cyclization of olefinic enones effectively compete with intramolecular [2 -I- 2]-cycloaddition to form spirocy-clic compounds [205, 206], 3-Alkenyloxy- and 3-alkenyl-2-cyclohexenones 235 are irradiated in the presence of triethylamine. As depicted in Scheme 46 two reaction pathways may operate. Both involve electron transfer steps, either to the starting material (resulting in a direct cyclization) or to the preformed cyclobutane derivative 239, which undergoes reductive cleavage. The second... 

Typically a hept-6-enyI radical will cyclize much slower than the corresponding hex-5-enyl radical, and often significant proportion of the primary radical is trapped before cyclization, and the olefinic product results. However, with the appropriate substituents or an activated acceptor, hepenyl radical cyclization can be used to prepare 6-membered carbocycles from carbohydrate precursors. For example, Redlich et al. [35] reported that 1,2-dideoxyhept-l-enitol derivatives can be cyclized to carbahexose derivatives [Eq. (II)]. Even though structural requirements (protecting groups, configuration of atoms in the carbon chain, and... 

Intramolecular addition of vinyl radicals to olefins as a method for heterocycle synthesis has been examined. The vinyl radicals can be conveniently generated from vinyl bromides and samarium(II) diiodide [95JOC7424], The intermediate radical after cyclization undergoes a further electron transfer from samarium to furnish a carbanion which is quenched at the end of the reaction. A samarium(II) diiodide mediated aryl radical cyclization onto a dihydrofuran has been reported [95T8555],... 

Eq. 3.20 shows the addition of Bu3Sn to thiocarbonyl sulfur of compound (61) to form carbon-centered radical, which cyclizes to olefinic group via 5-exo-trig manner to give thiollactone (62), after hydrolysis. 

Reductive radical cyclization and tandem radical addition/cyclization reactions catalyzed by Ni(II) complexes, such as Ni(cyclam)(C104)2 98a, were studied starting in the 1990s by Ozaki s group [128]. The reaction conditions are applicable to alkyl and aryl halides bearing suitable positioned olefin units. Iodides and bromides can be used in some cases even aryl chlorides were successfully applied. The field was reviewed recently, and thus only more recent results are summarized here [19, 20]. 

Cationic olefin cyclization as a key step led to the shortest racemic dendrobine synthesis reported so far (163, 164). Livinghouse et al. used an intramolecular acylnitrilium attack on a preformed methylcyclopentene moiety to construct the quaternary center and a reductive radical cyclization as second key step in a convergent synthesis to construct the fully substituted skeleton of dendrobine. A few additional steps led then to dendrobine (82). In most of the syntheses following Livinghouse efforts the intention was less focused on strategy (economy) of the synthesis of dendrobine (82) than on demonstrating the versatility of the (newly developed) key step. 

Bischof and Mattay have shown that radical anion cyclization leading to spirocyclic products compete effectively with intramolecular [2 -f 2]-cycloaddition on photoexcitation of olefinic enones in the presence of triethylamine [332, 333]. The [2 -f 2] cycloadducts could be converted to the corresponding spiro compounds under PET conditions (Scheme 75) [307]. 

Other interesting fused thiophene derivatives are prepared by radical mediated cyclizations. Tributyltin hydride treatment of bromide 69 produces the mixture 70 in 59% yield (trans cis = >5 1) <94TL5301>. Treatment of malonate 71 with various olefins and managanese (111) acetate produces 72. Examples of intramolecular cyclizadon are also reported < SC1493>. 

An alternative method to the commonly used [3+2] cycloaddition reaction was reported by Oshima and coworkers, where they demonstrated the synthesis of cyclopentane derivatives via a radical mediated cyclization [45]. This was achieved through the generation of a benzenethiyl radical, which subsequentiy led to the formation of substituted cyclopentanes via ring-opening of the vinyl-substituted cyclopro-panediester, followed by the addition of electron-rich and electron-poor olefins (Scheme 10.53 and Table 10.19). 

Many anodic oxidations involve an ECE pathway. For example, the neurotransmitter epinephrine can be oxidized to its quinone, which proceeds via cyclization to leukoadrenochrome. The latter can rapidly undergo electron transfer to form adrenochrome (5). The electrochemical oxidation of aniline is another classical example of an ECE pathway (6). The cation radical thus formed rapidly undergoes a dimerization reaction to yield an easily oxidized p-aminodiphenylamine product. Another example (of industrial relevance) is the reductive coupling of activated olefins to yield a radical anion, which reacts with the parent olefin to give a reducible dimer (7). If the chemical step is very fast (in comparison to the electron-transfer process), the system will behave as an EE mechanism (of two successive charge-transfer steps). Table 2-1 summarizes common electrochemical mechanisms involving coupled chemical reactions. Powerful cyclic voltammetric computational simulators, exploring the behavior of virtually any user-specific mechanism, have... 

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