Electrophilic radical

In the case of substituted aryl radicals, the results may be slightly different, depending on the polarity of the radicals. With electrophilic radicals the overall reactivity of the thiazole nucleus will decrease and the percentage of 5-substituted isomer (electron-rich position) will increase, in comparison with phenyl radicals. The results are indicated in Table III-28. 

CgH COO from BPO. The first type involves direct radical displacement on the oxygen—oxygen bond and is the preferred mode for nucleophilic radicals, eg, -CH(R)OR7 The second type involves radical addition to, or abstraction from, the hydrocarbyl group adjacent to the peroxide this is the preferred mode for electrophilic radicals, eg, Cl C (eq. 32). In the last type (eq. 33), there is hydrogen donation from certain hydrogen-donating radicals, eg, ketyls (52,187,188,199). 

The quiaones have excellent redox properties and are thus important oxidants ia laboratory and biological synthons. The presence of an extensive array of conjugated systems, especially the a,P-unsaturated ketone arrangement, allows the quiaones to participate ia a variety of reactioas. Characteristics of quiaoae reactioas iaclude nucleophilic substitutioa electrophilic, radical, and cycloaddition reactions photochemistry and normal and unusual carbonyl chemistry. 

The traditional means of assessment of the sensitivity of radical reactions to polar factors and establishing the electrophilicity or nucleophilieity of radicals is by way of a Hammett op correlation. Thus, the reactions of radicals with substituted styrene derivatives have been examined to demonstrate that simple alkyl radicals have nucleophilic character38,39 while haloalkyl radicals40 and oxygcn-ccntcrcd radicals " have electrophilic character (Tabic 1.4). It is anticipated that electron-withdrawing substituents (e.g. Cl, F, C02R, CN) will enhance overall reactivity towards nucleophilic radicals and reduce reactivity towards electrophilic radicals. Electron-donating substituents (alkyl) will have the opposite effect. 

However, consideration of polar factors in the traditional sense does not provide a ready explanation for the regiospecificity shown by the r butoxy radicals (which arc electrophilic, Tabic 1.3) in their reactions with the tluoro-olcfins (Tabic 1.2).22,23 Apparent ambiphilicity has been reported21 for other not very electrophilic radicals in their reactions with olefins and has been attributed to the polarizability of die radical. 

The rate of oxidation/reduction of radicals is strongly dependent on radical structure. Transition metal reductants (e.g. TiMt) show selectivity for electrophilic radicals (e.g. those derived by tail addition to acrylic monomers or alkyl vinyl ketones - Scheme 3.89) >7y while oxidants (CuM, Fe,M) show selectivity for nucleophilic radicals (e.g. those derived from addition to S - Scheme 3,90).18 A consequence of this specificity is that the various products from the reaction of an initiating radical with monomers will not all be trapped with equal efficiency and complex mixtures can arise. 

A consequence of the selectivity for electrophilic radicals is that not all products are trapped with equal efficiency. With electron-rich monomers (e.g. S) oligomerization may complicate analysis. Other possible complications in the utilization of this method have been discussed by Russell.491... 

The fraction of head-to-head linkages in the poly(fluoro-olefms) increases in the series PVF2 < PVF PVF3 (Tabic 4.2). This can be rationalized in terms of the propensity of electrophilic radicals to add preferentially to the more electron rich end of monomers (i.e, that with the lowest number of fluorines). This trend is also seen in the reactions of trifluoromethyl radicals wilh the fluoro-olefins (see 2.3). 

Thiols react more rapidly with nucleophilic radicals than with electrophilic radicals. They have very large Ctr with S and VAc, but near ideal transfer constants (C - 1.0) with acrylic monomers (Table 6.2). Aromatic thiols have higher C,r than aliphatic thiols but also give more retardation. This is a consequence of the poor reinitiation efficiency shown by the phenylthiyl radical. The substitution pattern of the alkanethiol appears to have only a small (<2-fokl) effect on the transfer constant. Studies on the reactions of small alkyl radicals with thiols indicate that the rate of the transfer reaction is accelerated in polar solvents and, in particular, water.5 Similar trends arc observed for transfer to 1 in S polymerization with Clr = 1.4 in benzene 3.6 in CUT and 6.1 in 5% aqueous CifiCN.1 In copolymerizations, the thiyl radicals react preferentially with electron-rich monomers (Section 3.4.3.2). 

The halocarbons react more rapidly with nucleophilic radicals than with electrophilic radicals. Thus, values of Cir with S and VAc are substantially higher than those with acrylic monomers ( fable 6.4) where the transfer constant is close to ideal (Clr=l.0). The haloalkyl radicals formed have electrophilic character (Section 2.3,2). 

In so far as the composition of the electrical effect is considered, the values of p given in Table XVll show that for both nucleophilic and electrophilic radicals, the resonance effect seems to predominate, probably in the case of the former and almost certainly in the case of the latter. 

In most known examples of catalyzed aromatic nucleophilic substitution (Sr I), the preliminary step aims at producing an aromatic electrophilic radical. Such electrophilicity is obtained, in general " , by substitution on the phenyl ring with a strongly electron-withdrawing substituent (E) which also activates the leaving of the other group (X) and the creation of a transient a radical. 

There are also reactions in which electrophilic radicals react with relatively nucleophilic alkenes. These reactions are exemplified by a group of procedures in which a radical intermediate is formed by oxidation of readily enolizable compounds. This reaction was initially developed for /3-ketoacids,311 and the method has been extended to jS-diketones, malonic acids, and cyanoacetic acid.312 The radicals formed by the addition step are rapidly oxidized to cations, which give rise to the final product by intramolecular capture of a carboxylate group. 

Entries 18 to 19 pertain to cyclizations of electrophilic radicals generated by oxidations. Entry 18 is the prototype for cyclization of a number of more highly substituted systems. The reaction outcome is consistent with oxidation of the less-substituted enolic position followed by a 6-endo cyclization. The cyclized radical is then oxidized and deprotonated. In Entry 19, the vinyl radical formed by cyclization is reduced by hydrogen abstraction from the solvent ethanol. 

The catalytic conditions are well suited for the preparation of cyclopropanes provided that a, /J-unsaturated carbonyl compounds are employed as radical acceptors (formation of electrophilic radicals after cyclization) as shown in Scheme 32 [123]. 

The behaviour of the frontier electrons was also attributed to a certain type of electron delocalization between the reactant and the reagent 40). A concept of pseudo-n-orbital was introduced by setting up a simplified model, and the electron delocalization between the 71-electron system of aromatic nuclei and the pseudo-orbital was considered to be essential to aromatic substitutions. The pseudo-orbital was assumed to be built up out of the hydrogen atom AO attached to the carbon atom at the reaction center and the AO of the reagent species, and to be occupied by zero, one, and two electrons in electrophilic, radical, and nucleophilic reactions. A theoretical quantity called "superdelocalizability was derived from this model. This quantity will be discussed in detail later in Chap. 6. 

Xanthates serve as a reliable source of electrophilic radicals, and this was exploited by Zard and coworkers for a short synthesis of ( )-matrine (3-304), a naturally occurring alkaloid which has been claimed to have anti-ulcerogenic and anticancer properties [116]. Heating a mixture of xanthate 3-299 and the radical acceptor 3-300 (3 equiv.) in benzene in the presence of lauroyl peroxide as initiator, gave 3-301 in 30% yield and a 3 1 mixture of the tetracylic products 3-302 and 3-303 in 18% yield (Scheme 3.76) [117]. The three compounds could be converted into the... 

The vanillin method is based on the condensation of the vanillin reagent with proanthocyanidins in acidic solutions. Protonated vanillin, a weak electrophilic radical, reacts with the flavonoid ring at the 6- or 8-position. The vanillin reaction is affected by the acidic nature and concentrations of substrate, the reaction time, the temperature, the vanillin concentration, and water content (Sun and others 1998). 

Based on the data collected in this section, one must conclude that the addition of radicals to dienes is certainly rapid enough to compete against the typical chain-breaking processes and that especially the addition of electrophilic radicals to polyenes appears to bear significant potential. Terminally substituted polyenes are likely to be unsuitable for radical addition reactions due to their lower addition rates and to undesirable side reactions. 

The orbital coefficients obtained from Hiickel calculations predict the terminal position to be the most reactive one, while the AMI model predicts the Cl and C3 positions to be competitive. In polyenes, this is true for the addition of nucleophilic as well as electrophilic radicals, as HOMO and LUMO coefficients are basically identical. Both theoretical methods agree, however, in predicting the Cl position to be considerably more reactive as compared to the C2 position. It must be remembered in this context that FMO-based reactivity predictions are only relevant in kinetically controlled reactions. Under thermodynamic control, the most stable adduct will be formed which, for the case of polyenyl radicals, will most likely be the radical obtained by addition to the C1 position. 

Radical hydroxylation of hydrocarbons by autooxidation yields alcohols (major products), ketones, and acids (minor products). Cyclohexanol, for example, is formed in 90% yield from cyclohexane and peroxyacetic acid (275). The high -ol/-one ratio at low conversions can sometimes be used as a partial diagnostic tool to distinguish between the radical and electrophilic pathways. The predominant reaction of electrophilic radicals, such as HO, ROO, and CH 3 is H-atom abstraction from reactants (S-H) or peracids, as exemplified by the following ... 

Carbon dioxide, shown to be an ideal medium for reactions involving very electrophilic radicals,31,43 has also been shown to be useful in the photooxidation of fluorinated olefins in the synthesis of PFPEs.4 Table 13.4 shows some representative results of the photooxidation of HFP in liquid C02. Overall, the resulting products of photooxidations in liquid C02 are similar to those... 

The electron-withdrawing substituent when present in a free radical makes it more electrophilic, and electrophilic radical will seek a monomer containing an electron-releasing substituent and vice versa. 

Silyl enol ethers have also been used as a trap for electrophilic radicals derived from a-haloesters [36] or perfluoroalkyl iodides [32]. They afford the a-alkylated ketones after acidic treatment of the intermediate silyl enol ethers (Scheme 19, Eq. 19a). Similarly, silyl ketene acetals are converted into o -pcriluoroalkyl esters upon treatment with per fluoro alkyl iodides [32, 47]. The Et3B/02-mediated diastereoselective trifluoromethylation [48,49] (Eq. 19b) and (ethoxycarbonyl)difluoromethylation [50,51] of lithium eno-lates derived from N-acyloxazolidinones have also been achieved. More recently, Mikami [52] succeeded in the trifluoromethylation of ketone enolates... 

Anodic addition of nucleophiles to olefins can be achieved via oxidation of the alkene to a radical cation.This means that a nucleophile can be added to a nucleophilic alkene by reversing its polarity to an electrophilic radical cation... 

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