Radical stereoselectivity

The Kochi reaction has also been used to demonstrate polar effects of remote substituents upon free-radical stereoselectivities in chlorine atom transfer. ... 

Tetrahydrofurans are known to be less conformationally rigid than their 6-membered ring counterparts, and hence anomeric effects in these systems also tend to be less pronounced. In the reactions of 2-tetrahydrofuranyl radicals, stereoselectivities tend to be dictated by steric rather than electronic effects [13]. With respect to C-1 nucleoside radicals, both Tanaka and Chatgilialoglu have independently reported methods for forming these species via 1,2-acyloxy migration and... 

Also, it was demonstrated that acyclic radicals can react with high stereoselectivity [45]. In order for the reactions to be stereoselective, the radicals have to adopt preferred conformations where the two faces of the prochiral radical centers are shielded to different extents by the stereogenic centers. Giese and coworkers [49] demonstrated with the help of Electron Spin Resonance studies that ester-substituted radicals with stereogenic centers in (3-positions adopt preferred conformations that minimize allylic strain [49] (shown below). In these conformations, large (L) and medium sized substituents (M) shield the two faces. The attacks come preferentially from the less shielded sides of the radicals. Stereoselectivity, because of A-strain conformation, is not limited to ester-substituted radicals [50]. The strains and steric control in reactions of radicals with alkenes can be illustrated as follows [50] ... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The stereoselectivity of the radical addition can be explained in terms of a bridged structure similar to that involved in discussion of ionic bromination of alkenes ... 

Analogous reactions under free-radical conditions show a preference for the erythro isomer when X = Cl, however when X = tnfluoromethyl, the reaction shows essentially no stereoselectivity [S] (Table 3)... 

Radical cyclization of perhydro-l,3-benzoxazines 64, promoted by Bu4SuH in the presence of AIBN gave a mixture of perhydropyrido[2,l-6][1,3]benzoxazin-9-ones 65 and 66 and seven membered tricyclic derivatives 67 and 68, formed in a 6-exo and 7-endo cyclization process, respectively (99TL2421). Cyclization of parent acrylamide 64 (R = R = H) occured with moderate regioselectivity (6-exo/7-endo ratio 65 35) and poor stereoselectivity (65/66 ratio 42 43). The presence of a /3-methyl group in... 

Stereoselective preparation of CEi-allyl alcohols via radical elimination from ruin -y-phenylthio-fi-nkro alcohols has been reported. The requisiteruin -fi-nitro sulfides are prepared by protonadon of nitronates at low temperanire Isee Chapter 4, and subsequent treatment v/ith Bu-vSnH induces and eliminadon to givelE -alkenes selecdvely IseeEq. 7.112. Unfortunately, it is difficult to get the pure syu-fi-nitro sulfides. Treatment of a rruxnire of syu- and ruin -fi-nitrosulfides v/ith Bu- SnH results in formadon of a rruxnire of (Ey and lZ -alkenes. 

In an effort to identify a more stereoselective route to dihydroagarofuran (15), trimethylsilylated alkyne 17 was utilized as a substrate for radical cyclization (Scheme 2). Treatment of 17 with a catalytic amount of AIBN and tri-n-butyltin hydride (1.25 equiv) furnishes a mixture of stereoisomeric vinyl silanes 18 (72% combined yield) along with an uncyclized reduction product (13% yield). The production of stereoisomeric vinyl silanes in this cyclization is inconsequential because both are converted to the same alkene 19 upon protodesiiyiation. Finally, a diastereoselective di-imide reduction of the double bond in 19 furnishes dihydroagaro-... 

The wide variety of methods available for the synthesis of orga-noselenides,36 and the observation that the carbon-selenium bond can be easily cleaved homolytically to give a carbon-centered radical creates interesting possibilities in organic synthesis. For example, Burke and coworkers have shown that phenylselenolactone 86 (see Scheme 16), produced by phenylselenolactonization of y,S-unsaturated acid 85, can be converted to free radical intermediate 87 with triphenyltin hydride. In the presence of excess methyl acrylate, 87 is trapped stereoselectively, affording compound 88 in 70% yield 37 it is noteworthy that the intramolecular carbon-carbon bond forming event takes place on the less hindered convex face of bicyclic radical 87. 

Similar stereoselectivities are achieved in the allylation of enantiomerically pure proline-derived a-oxoamides47. l-Bromo-3-methy]-2-butcne reacts with clean allylic inversion. Since pinacol-type coupling products are also produced under the reaction conditions, this was taken as evidence for a radical addition mechanism47. 

Most radicals located on saturated bonds are jt-radicals with a planar configuration and may be depicted with the free spin located in a p-orbital (1). Because such radical centers are achiral, stereochemical integrity is lost during radical formation, A new configuration will be assumed (or a previous configuration resumed) only upon reaction. Stereoselectivity in radical reactions is therefore dependent on the environment and on remote substituents. 

Metalloporphyrins as catalysts of chain transfer in radical polymerisation and stereoselective oxidation. L. Karmilova, G. V. Ponomarev, B. R. Smirnov and I. M. Bel yovskii, Russ. Chem. Rev. (Engl. Transl), 1984, 53,132 (44). 

These results are in accordance with the findings of Boothe and coworkers26, who found that the reactions of four diastereomeric 2-bromo-3-phenylsulfinylbutanes with tributyl-tin radicals generate /3-phenylsulfinyl sec-butyl radicals (8) which eliminate PhSO radicals to form the 2-butenes in a stereoselective manner. The stereoselectivities observed in this free radical elimination must result from the fact that the rate constant for elimination is greater than that for rotation about the C—C bond. Furthermore, a neighboring phenyl group on the radical center seems to stabilize the radical enough so that the internal rotation can compete with the -elimination reaction. It is also noteworthy that the small... 

In the thermal reaction of aliphatic and aromatic sulfonyl chlorides with acetylenes no adduct has been observed82. However, the light-catalyzed additions of sulfonyl iodides to acetylenes83 as well as the thermal addition of sulfonyl bromides to phenylacetylene84 to form 1 1 adducts have been shown to be stereoselective and to occur in good to excellent yields. The fact that the addition occurs in a trans manner forced the authors83,84 to suggest that chain transfer by the sulfonyl halide (k ) is much faster than isomerization of the intermediate vinyl radical (k2) (see Scheme 5). 

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