Hex-5-enyl radicals

Moreover, the reaction with Y = OCH3 and the stereochemical control of analogous hex-5-enyl radical cyclizations has also been studied. This method constitutes part of a synthetic route from carbohydrates to optically active carbocycles.[74],[75]... 

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... 

Radical cyclization reactions provide a good example of the situation where kinetic and thermodynamic products appear to differ. Cyclization of hex-5-enyl radical can either yield cyclopentylmethyl radical or cyclohexyl radical. 

Organic chemists have a keen eye for what is stable and what is not. For example, they will easily recognize that cyclohexyl radical is more stable than methylcyclopentyl radical, because they know that "6-membered rings are better than 5-membered rings", and (more importantly) that "2° radicals are better than 1° radicals". However, much important chemistry is not controlled by what is most stable (thermodynamics) but rather by what forms most readily (kinetics). For example, loss of bromine from 6-bromohexene leading initially to hex-5-enyl radical, results primarily in product from cyclopentylmethyl radical. ... 

Of all the radical reactions, the exo-l,5-cycIization of a hex-5-enyl radical to cyclopen-tylmethyl radical and its subsequent trapping by various reagents have attracted the most attention from synthetic chemists (Scheme 1) [4-7]. Starting materials that are most often used for the tin method (initiation of the chain by trialkyl tin radical) are halides, sulfides, selenides, or thionocarbonates. The generation and cyclization of the radical proceeds under exceptionally mild neutral conditions, and these conditions are compatible with a wide variety of common functional groups. A prototypical example of an application in carbohydrate chemistry is shown in Scheme 2 [8]. Readily available 2,3-di-O-isopropyl-ideneribonolactone 1 was converted into the bromoacrylate 2 in three steps. Radical... 

A versatile protocol for the generation and cyclization of secondary radicals from hexo-pyranose sugars is shown in Scheme 3 [10], The Wittig reaction of reducing sugars with two eq of an alkylidene phosphorane readily provide hex-5-ene-l-ols, which were converted into hex-5-enyl radicals by the l-ff-imidazole-l-carbothioate. The cyclization reaction is carried out in refluxing benzene or toluene with tributyltin hydride and AIBN, according to... 

Scheme 4 Transition-state models for sugar hex-5-enyl radical cyclizations.7...

This stereochemical control in hex-5-enyl radical cyclizations can be used for the synthesis of highly functionalized cyclopentanes with vicinal trans- or cis-dialkyl-substituents. The synthesis of a versatile prostaglandin intermediate, Corey lactone 12, from the intermediate 6a (Y = OMe) has been described [14]. 

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... 

A. Carbocycles from Unsaturated Halo Sugars by Hex-5-enyl Radical Cyclizatlon [8]... 

T. V. RajanBabu, From carbohydrates to optically active carbocycles, 1 Stereochemical control in sugar hex-5-enyl radical cyclization, J. Am. Chem. Soc. 109 609 (1987). 

Well-known "Beckwith transition states in which a maximum number of groups are in an equatorial orientation of a chair-like transition state provides a satisfactory rationalization for the formation of the products. A. L. J. Beckwith, C. J. Easton, T. Lawrence, and A. K. Serelis, Ausi. J. Chem. 36 545 (1983) see also D. C. Spellmeyer and K. N. Houk, A force field model for intramolecular radical additions, J. Org. Chem. 52 959 (1987) T. V. RajanBabu and T. Fukunaga, Stereochemical control in hex-5-enyl radical cyclizations Axial vs. equatorial 2-(but-3-enyl)cyclohexyl radicals, J. Am. Chem. Soc. Ill 296 (1989). 

In less reactive 6-fluorohex-1-ene (19), the nonactivated sp3 C-F bond reacts with sodium naphthalenide in tetrahydrofuran to give a complex mixture of acyclic and cyclic nonfluorinated products.28 The intermediate hex-5-enyl radical cyclizes to the methylcyclopentyl radical, and both are reduced further with the naphthalenide to the corresponding anions before forming the products.29 30... 

The authors reported that methyl 4-mercapto-2-alkenoates 710, obtained by irradiation of 2(5H)-thiophenones 709 in MeOH, undergo light-induced S-H bond homolysis to give thio radicals 710 (84HCA2198 85HCA2350 87HCA125). Intermediate 710 can be trapped by alkenes to afford 3-thia-hex-5-enyl radical 711, which cyclize selectively to radicals 712, precursors of thiolane-3-acetates 714. 

Thiopyrans are produced in high yield by the microwave-induced one-pot reaction between a,/ -unsaturated ketones, dienophilic alkynes, and Lawesson s reagent. The equivalent thermal reaction is unsuccessful <2006TL4925>. Calculations at the G3MP2B3 level show that the introduction of a 5-methyl substituent into n -sul I cnyl-. a-sulfinyl-, and ct-sulfonyl- hex-5-enyl radicals shifts the regioselectivity of cyclization to the 6-endo products, tetrahydrothiopyran derivatives <2006JOC9595>. 

There are exceptions to this pattern, most of them in cyclisation reactions. Hex-5-enyl radicals 7.26 (R1 = R2 = H) cyclise to give the less stable, primary radical 7.25 (R1 = R2 = H) with a selectivity of 98 2. 

A. Carbocycles from unsaturated halo sugars by hex-5-enyl radical cyclization 558... 

Another striking reversal of the rule is in the cyclization of hex-5-enyl radicals (396). Generally, these cyclize contrathermodynamically to give the primary radical (397). This may be for all sorts of reasons, but it is noteworthy that cylization to the secondary radical (395) does take place when the groups R and R are electron-withdrawing.315... 

The most favourable approach for attack by a radical appears to be along the line on which the new bond is being formed (Figure 6.7). For the intramolecular addition of the hex-5-enyl radical 49, this results in the formation of the less stable primary cyclopentylmethyl radical 50 by reaction (6.37) rather than the more stable secondary cyclohexyl radical 51 by reaction (6.38). 

The cyclization of hex-6-enyl radicals proceeds much more slowly than that of hex-5-enyl radicals, and consequently reduction or 1,5-hydrogen abstraction may occur before cyclization. Preparations of cyclohexanes by 6-exo-cyclization of hex-... 

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