Biological Additions of Radicals to Alkenes

One of the chain-termination steps tliat sometimes occurs to interrupt polymerization is the following reaction between two radicals. Propose a mechanism for the reaction, using fishhook arrows to indicate electron flow. 

The same high reactivity of radicals that makes possibit the alkene polymerization we saw in the previous section also makes it difficult to carry out controlled radical reactions on complex molecules. As a result, there are severe limitations on the usefulness of radical addition reactions in the laboratorv. In contrast to an electro-/j/z/Z/c addition, where reaction occurs once and the reactive cation intermediate is rapidly quenched in the presence of a nucleophile, the reactive intermediate in a railictil reaction is not usual) quenched, so it reacts again and again in a largely uncontrollable wav. 

Electrophilic addition (Intermediate i quenched, so reaction stops  

Radical addition (Intermediate is not quenched, so reaction does not stop.] 

In biological reactions, the situation is different from that in the laboratory. Only one substrate molecule at a time is present in the active site of the enzyme where reaction takes place, and thal molecule is lield in a precise position, with coenzymes and other necessary reacting groups nearby. As a result, biological radical reactions arc both more controlled and more commmi than laboratorv or industrial radical reactions. A particularly impressive example occurs in the bio.synthesis of prostaglandins from arachidunic acid, wlicrc a sequence of four radical additions take place. The reaction mechanism was discussed briefly in Section 5.3. 

Natural rubber is obtained from the bark of the rubber tree, Hevea brasiliensis, grown on enormous plantations in Southeast Asia. 

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Chapter 7, Alkenes Reactions and Synthesis—Alkene epoxidation has been moved to Section 7.8, and Section 7.11 on the biological addition of radicals to alkenes has been substantially expanded. 

The observation that thiyl radicals are able to isomerize alkenes was first made by Walling et al. many years ago [55] and, now the addition-elimination sequence of the phenylthiyl radicals is an established methodology in fine chemical synthesis [56]. It has been utilized as key step in the synthesis of biologically active compounds, such as (-)-gloeosporone [57a], (-l-)-hitachimycin [57b] and other naturally occurring macrolides [5b], as well as for preparing non-natural isomers of phospholipids [58]. 

Chapter 13 discusses the substitution reactions of alkanes— hydrocarbons that contain only single bonds. In previous chapters, we have seen that when a compound reacts, the weakest bond in the molecule breaks first. Alkanes, however, have only strong bonds. Therefore, conditions vigorous enough to generate radicals are required for alkanes to react. Chapter 13 also looks at radical substitution reactions and radical addition reactions of alkenes. The chapter concludes with a discussion of some radical reactions that occur in the biological world. 

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