Electron-deficient radicals

A novel aromatic substitution reaction with electron-deficient radicals, which avoids the use of stannanes, is promoted by the addition of tetra-n-butylammonium bromide [54]. Iodoacetonitrile and iodoacetic esters react with pyrroles and indoles in good to high yield upon photolysis in the presence of 2-methyloxirane and sodium thiosulphate (Scheme 6.34). 

In an extension of atom-transfer radical reactions to heterocyclic systems, Byers has introduced a novel methodology for the addition of electron-deficient radicals to unprotected pyrroles and indoles in a stannane-fi ee, non-oxidative process <99TL2677>. For exanqrle, photochemical reaction of pyrrole (33) with etl l iodoacetate (34) in presence of thiosulfiite as an iodine reductant, phase transfer catalyst and propylene oxide led to high yields of the 2-alkylated pyrrole 35 <99TL2677>. 

The coupling reaction by which the aromatic group from one residue of mono- or diiodotyrosine is joined in ether linkage with a second residue is also catalyzed readily by peroxidases. One dehydroalanine residue is formed for each molecule of hormone released.108 A possible mechanism involves formation of an electron-deficient radical, which can undergo (3 elimination to produce a dehydroalanine residue and an aromatic radical. The latter could couple with a second radical to form triiodothyronine or thyroxine. However, as depicted in Eq. 25-6, the radical coupling may occur prior to chain cleavage. While P elimination (pathway... 

Such structures may not be the principal contributors to the resonance hybrid, but they do convey the idea that charge transfer from nitrogen to oxygen tends to crowd the triplet character into the intervening aromatic nucleus, thus virtually destroying any electron-deficient radical-like character of the carbonyl oxygen. 

The dominant factor that gives rise to the observed high reactivities of per-fluoro-n-alkyl radicals, particularly in their additions to electron-rich alkenes, would appear to be the high electrophilicities of these very electron-deficient radicals [114]. A perfluoro-n-alkyl radical, which one can assume to have a low-lying SOMO, should exhibit a dominant SOMO-HOMO interaction in its additions to alkenes, and polarization of the type shown in Fig. 1 will stabilize the early transition state in which little radical character has been transferred to the substrate alkene. Therefore, if steric hindrance is equivalent for a series of alkenes, the rates of addition of RF should correlate with the alkene IPs (which should reflect HOMO energies). As Fig. 2 indicates, there is indeed a respectable correlation between log kadd for typical perfluoro-n-alkyl radicals and terminal... 

We now turn our attention to the second common reaction of radicals, addition to double bonds. Because an alkene contains an electron-rich, easily broken n bond, it reacts with an electron-deficient radical. 

It was found that a variety of radical precursors could be added, and that the specific electronic and steric effects exerted on the resulting radical effected the diastereoselectivity of the hydrogen atom transfer. Increasing the size of R group appeared to increase the selectivity of the trap. For instance, reaction with t-butyl radical and tributyltin hydride gave the highest selectivity, >98 2 (70% yield), for the trans product (77). Reactions with electron-deficient radicals suffered from low yields and decreased selectivity. Results also indicate that reactions with tributyltin hydride produced higher selectivities but lower yields than those per-... 

An example of 1,3-asymmetric induction has been illustrated in the copper-mediated addition of electron-deficient radicals to alkenes [48]. The reaction is shown as in Eq. (13.36). The mechanism involves a single-electron transfer from copper, which forms the copper(I) halide as a by-product. This reaction also uses atom-transfer methodology to obtain halogen transfer at the y position (116), which then readily lactonizes with the ester to form the product 117. 

In Chapter 25, Russell and Khanna examine a novel class of nucleophilic reactions, reaction with radicals. The specific reaction is that of unsaturated anions (e.g., R2C=CO-C6H5) with radicals to give relatively stable anion radicals. Rates are obtained for the reactions, and some novel substituent effects are observed. The reactions of electron-rich (CH3)3C are especially interesting in that here the more basic nucleophiles are actually the slower to react. On the other hand, more normal nucleophilic behavior is seen for electron-deficient radicals (such as C6H5COCH2 ), where an increase in basicity of the anion leads to an increase in rate. 

The mechanism proposed by them is based on the reaction of a SOMOphilic enamine 3 with an electron-deficient radical, which is the converse mechanism to their previously reported SOMO activation studies [33]. It is noteworthy that the present catalytic system can allow us an easy access to various optically active a-alkylated aldehydes 4 in high yields with excellent enantioselectivity. 

We have seen that increasing the substitution around a radical is a stabilizing influence. We called this an inductive ect, which means that the alkyl substituent donates electron density to the electron-deficient radical center. We often say that inductive effects are through-bond effects, as if the bond were a wire of sorts through which electron density can be transferred. Let s consider the rm-butyl radical. It is very nearly planar, and it has a half-filled 2p orbital on the tertiary carbon. 

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