Radical reactions regioselectivity

The regioselectivity of addition of Itydrogen bromide to alkenes can be complicated if a free-radical chain addition occurs in competition with the ionic addition. The free-radical reaction is readily initiated by peroxidic impurities or by light and leads to the anti-Markownikoff addition product. The mechanism of this reaction will be considered more fully in Chapter 12. Conditions that minimize the competing radical addition include use of high-purity alkene and solvent, exclusion of light, and addition of free-radical inhibitors. ... 

The final stage of the reaction in Scheme 3.65 involves protonation, yielding the derivative of 1,4-dihydronaphthalene. The oxidation may produce a 4-substituted binaphthyl, which is not contaminated with the isomeric products. It is worth noting here that the described ion-radical method of introduction of the alkyl group into the aromatic nucleus has an advantage over the radical or heteroly tic alkylation. In these cases, the neutral substrate may produce a composite mixture of isomeric products. The binaphthyl anion-radical reaction proceeds regioselectively and nonstereospecifically. 

Meldrum s acid, like other 1,3-dicarboxyl compounds, was amenable to radical reactions at C-5. The radical reaction between Meldrum s acid benzyl alkyl ethers mediated by InCl3/Cu(OTf)2 has been reported to proceed regioselectively at the benzylic position of the ether moiety (Scheme 35) <2006AGE1949>. Radical reaction of Meldrum s acid and alkenes was carried out with 2equiv of ceric ammonium nitrate (CAN) to give the a-carboxy-lactones which were subsequently subjected to decarboxylative methylenation affording the a-methylene lactones in 35-50% yield (Scheme 35) <2006SL1523>. 

Alkyl radicals, prepared in situ, react with pyridine to form mainly 2-alkyl derivatives and this regioselectivity is shown in the free radical reactions of alkylmercurial compounds with pyridines (Scheme 37). 

Free-radical reactions, for so long the Cinderellas of organic chemistry because of lack of control over their selectivity, have in recent years frequently emerged as simple, efficient, and novel means for effecting molecular transformations, and they are now at the forefront of synthetic methods. Previous emphasis was on the physicochemical investigations of reactions from which developed appreciation of such factors as the regioselectivity of... 

The position selectivity is observed in those cases where a nonsymmetrically substituted diene acts as a dienophile. The more substituted double bond is involved in an ion radical reaction, which develops according to Scheme 6-16. This scheme makes understandable the regioselectivity observed. Such regioselectivity is possible when both the diene and the dienophile are nonsymmetrically substituted. Then dimerization can be of the head-to-head type, with the formation of 1,2-disubstituted derivatives of cyclohexene, or the... 

Stereospecificity manifests itself in the dimerization of a diene with a diene. The double bond that remains free may deviate from the ring formed (exo configuration) or may approach it (endo configuration). Endo condensation is the predominant pathway in the case of ion radical reactions (Scheme 6-17). As seen, the charge distribution in the reactants dictates the head-to-tail pathway of the reaction. For the cation radical, the position selectivity at the C(l) atom is 100%, regioselectivity being 0%, whereas at the C(4) atom the position selectivity is 0% and regioselectivity is 100%. In other words, only the addition of the D+ -C(l) + D°-C(4) type is observed (symbol D° refers to a neutral diene and D+ to a diene in cation radical form). 

The radical reaction of hydrazine and methylhydrazine with some a,(3-unsaturated ketones 54 initiated by 2,2-dipenyl-l-picrylhydrazyl (DPPH) is described in [60]. At — 78°C the treatment is practically regioselective and yields pyrazoles 55, while regioisomeric heterocycles 56 are observed in trace amounts (Scheme 2.13). 

Thermal addition of SXC12 to fluoroolefins was often referred to as electrophilic addition [136, 137], although observed orientation of addition actually resembles that in radical reactions [139], Regardless of the mechanism, this reaction is highly regioselective and undoubtedly has synthetic value as a high yield route to polyfluoroalkyldisulfides. 

Irradiation of purines in different environments can, of course, lead to a variety of radical reaction products. Recently the regioselective nature of radical methylation has been observed in several purine derivatives. 

Asymmetric Radical Reactions. Several reports have documented the utility of nonracemic fra/w-2,5-dimethylpyrrolidine as a chiral auxiliary in asymmetric radical reactions. For example, the addition of -hexyl, cyclohexyl, and f-butyl radicals to the chiral acrylamide of 4-oxopentenoic acid provided four diastere-omeric products resulting from a- and p-addition (eq 7). The isomers resulting from p-addition were formed with no diastereoselectivity however, the isomers resulting from a-addidon were formed in ratios of 16 1,24 1, and 49 1. Unfortunately, the application of this chemistry is limited due to the poor regioselectivity in the addition and difficulty in removal of the chiral auxiliary. 

Radical reactions generally offer versatile alternatives to ionic reactions [167]. Many methods have been developed that allow chemoselective and regioselective radical transformations. More recently, stereoselective radical reactions have been reported [168]. 

A. L. J. Beckwith, Regioselectivity and stereoselectivity in radical reactions. Tetrahedron 37 3013 (1981). 

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