Radical-mediated reactions

Radical reactions can often be rationalized on the basis of frontier orbital considerations for intermediate radical species, the reactivity and stereochemistry of which can certainly be regulated with Lewis acid additives [21-23]. The first appearance of Lewis acids in radical reactions was in polymerization reactions resulting in alternation of copolymers different from that obtained without Lewis acids [24-26]. This concept, Lewis acid-directed radical reactions, has been applied to reductions and alkylations of organic halides or olefins, and has resulted in highly stereospecific processes. 

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The destruction of contaminants has directed attention to the use of hydroxyl radical-mediated reactions. These reactions should be viewed against those with hydroxyl radicals that occur in the atmosphere. 

Compared with the extensive application of NMR procedures, electron paramagnetic resonance (EPR) is used less frequently except for analysis of the state of metals in enzymes and coenzymes. There has, however, been increasing awareness of the role of radical-mediated reactions and some examples are used to illustrate its potential. 

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

The chemistry and utility of zinc-based Lewis acids are similar to those of their magnesium analogs. Their mild Lewis acidity promotes several synthetic reactions, such as Diels-Alder reactions, hetero Diels-Alder reactions,229 radical-mediated reactions,230 ene-type cyclization, and Simmons-Smith reactions. 

THEMES Free Radical-Mediated Reactions Lewis Acid, Transition Metal-Mediated Reactions... 

G. Stork, H. S. Suh, and G. Kim, The temporary silicon connection method in the control ol regio- and stereochemistry. Application to radical-mediated reactions. The stereospecific synthesis of C-glycosides, J. Am Chem. Soc. 7/3 7054 (1991). 

The aim of the present article is to survey a radical-mediated reaction by which bromine atoms may be substituted directly into some carbohydrate derivatives at ring positions by the following general mechanism. 

The survey is intended to cover the published literature on the subject as fully as possible. Although the four halogens are well known as constituents of a wide range of carbohydrate compounds, radical-mediated halogenations have, in most cases, been realized only with bromine. There are, however, some examples of chlorinations to the best of our knowledge, there are no reported fluorinations or iodinations which occur by direct, radical-mediated processes. The radical-mediated reactions by which bromodeoxy carbohydrates are obtainable from benzylidene acetals17-19 are not considered. 

The synthetic procedures available to the carbohydrate chemist have been largely dominated by standard reactions proceeding by heterolytic processes within a chiral matrix. The preparative utility of radical-mediated reactions has, however, been amply demonstrated in recent years. The chapter contributed here by L. Somsak (Debrecen) and R. J. Ferrier (Wellington), on bromination reactions of carbohydrates proceeding by radical processes integrates the literature related to Ferrier s pioneering work in this area and underscores its excellent potential in synthesis. 

The lipoxygenase system also competes for released arachidonic acid in a way that seems to be tissue-selective, giving rise to hydroperoxy fatty acids (HPETE) which can be converted into leukotrienes or reduced to hydroxy fatty acid (HETE) products [115]. The basic scheme for these metabolic conversions involving arachidonic acid is presented in Figure 5.2. Both of the main enzymatic pathways of arachidonic acid metabolism are thought to involve free-radical-mediated reactions [108] and the antioxidant capacity of vitamin E could therefore allow the vitamin to modify the products of these pathways. 

Free-radical-mediated reactions have clearly been shown to be a powerful means of connecting three and more components into one molecule. The diversity of examples presented in this chapter provides ample proof for the utility of radical-... 

Although Fenton did not observe hydroxyl radical-mediated reactions for mixtures of Fe3+ and hydrogen peroxide, more recent work has illustrated that such systems can produce hydroxyl radical. Haber and Weiss [5] originally proposed a free radical mechanism for the Fe3+-catalyzed decomposition of hydrogen peroxide. These reactions include [3] ... 

Radical-mediated reaction of 7-hydroxy or 7-alkoxy-a-methylene ester (21) with iso-Prl in the presence of MgBr2 gives the yyrc-adduct (22a) predominantly via the intermediate [V] as shown in eq. 10.11. The same chelation-controlled radical 1,3-stereo... 

A cycloaddition methodology has been exploited in the cation radical-mediated reactions between electron-rich chalcone epoxides 287 and A -aryl imines 286 using tris(4-bromophenyl)aminium hexachloroantimonate (TBPA -SbCle ) as the radical initiator to generate substituted 1,3-oxazolidines 288a and 288b in good yields (Equation 21) <2005SL161>. 

Radical SAM (S-adenosyl methionine) enzymes utilise iron—sulfur clusters and SAM to initiate a diverse set of radical-mediated reactions. 

Radical-mediated reaction of a radical precursor tetrahydroisoquinoline derivative has been found to produce the 5,11-methanomorphanthridine ring system 182). Thus, a formal total synthesis of this type of alkaloid was performed by means of the present methodology. Namely, the reaction of l,2,3,4-tetrahydro-A -(4-oxocyclohex-2-enyl)-4-phenylthioisoquinoline (357) with BusSnH in boiling o-xylene containing AIBN led to 5,11-methanomorphanthridin-2-one (358) in 80% yield, which was transformed to A -5,ll-methanomorphanthridine 359 by way of a mesate. In continuation, 359 provided the 2,3-O-benzylidene derivative 349 in two steps (OSO4 oxidation and O-benzylidenation), which was previously 179) converted into this type of alkaloid (Scheme 37). 

As in vitro methods for studying cytochrome P-450 in insects became available (11-131, it soon became clear that insects with high cytochrome P-450 activities were resistant to carbamates and most other insecticides. This phenomenon is termed metabolic cross resistance and derives from the characteristic of cytochrome P-450 of accepting a very wide range of molecular structures as substrates the cytochrome binds the substrate very loosely by a lipophilic interaction and rapidly oxidizes it by an oxygen free radical-mediated reaction, a very powerful combination. Moreover, the cytochrome occurs in several or many different isoenzymic forms with broadly overlapping substrate preferences. A normally infrequent form may be selectively induced by allelochemicals in the crop plants (14), and if the induced form has survival value in the presence of an insecticide, it could be selected to dominate in the exposed population (15). 

Hydroxy sulfones can be easily transformed into derivatives for radical-mediated reactions such as thiobenzoates,220 xanthates,221,222 selenoben-zoates,221,222 and thionocarbonates.221,222 These substrates may be used in subsequent stereoselective syntheses of alkenes by free radical methods. Methyl xanthates usually give the best results in the olefination reaction, typically using O-acyl A - It y d roxy- 2 - thiopy ri d o n e under visible light irradiation. Alternatively, diphenylsilane in combination with radical initiators such as Et3B/02, benzoyl peroxide, or AIBN may also be used (Eq. 127).221 222... 

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