Radicals stereoelectronic effects

The relatively low rate and high activation energy noted for entry 32 also reflect a stereoelectronic effect. The preference for delocalization at the radical center requires... 

The most direct evidence that stereoelectronic effects are also important in these reactions follows from the specificity observed in hydrogen atom abstraction from conformationally constrained compounds,18 60 C-H bonds adjacent to oxygen113"118 or nitrogen110 and which subtend a small dihedral angle with a lone pair orbital (<30°) are considerably activated in relation to those where the dihedral angle is or approaches 90°. Thus, the equatorial H in 20 is reported to be 12 times more reactive towards /-butoxy radicals than the axial 11 in 21.115... 

A further example of the importance of this type of stereoelectronic effect is seen in the reactions of /-butoxy radicals with spiro[2,n]alkanes (22) where it is found that hydrogens from the position a- to the cyclopropyl ring arc specifically abstracted. This can be attributed to the favorable overlap of the breaking C-H bond with the cyclopropyl cr bonds.120131 No such specificity is seen with bicyclo[n, 1,0]alkanes (23) where geometric constraints prevent overlap. 

Stereoelectronic effects can be invoked for the radical reaction at anomeric centre of carbohydrates. The high stereoselective preparation of a-substituted C-glycosyl phosphonates in a a p ratio of 98 2 was achieved by reductive addition of bromide 2 to a-phosphonoacrylate (Reaction 7.5) [10]. Yields (in parentheses) depend on the sugar configuration D-galacto (80%), D-manno (47 %), D-gluco (30 %) and L-fuco (62 %). 

This different behavior can be explained by the conformation of the radicals and by stereoelectronic effects [6]. Electron spin resonance (ESR) investigations have revealed that the D-glucopyranosyl radical 7 does not adopt the 4C1 conformation 7a, but is distorted into the B2 5 shape 7b (Scheme 5) [7,8], The equatorial-like attack at the boat conformer... 

In contrast, the mannosyl radical 8 does not undergo such a conformational change, and the observed a-attack results from the shielding effect of the axial C-2 substituent in the chair conformation and the stereoelectronic effects mentioned earlier. In radicals 7b and 8 the C-O bonds adjacent to the radical center are coplanar with the singly occupied orbital. This reminds us of the anomeric effect in which an interaction between the nonbonding electron pair of the ring oxygen and the LUMO of the C-O bond stabilizes the conformation. 

Gilbert BC, Lindsay Smith JR, Taylor P, Ward S, Withwood AC (1999) The interplay of electronic, steric and stereoelectronic effects in hydrogen-atom abstraction reactions of S04, revealed by EPR spectroscopy. J Chem Soc Perkin Trans 2 1631-1637 Flasegawa K, Neta P (1978) Rate constants and mechanisms of reaction of Cl2 radicals. J Phys Chem 82 856-859... 

The knowledge of photoreaction mechanisms and of the structures of intermediate radicals is also of particular interest in the understanding of many structural modifications of sugars. For instance, radicals which are not solvated and less susceptible to steric factors adopt specific conformations determined by stereoelectronic effects which can explain some regio and stereoselectivities of many photochemical reactions in carbohydrates. 

All these syntheses of non-anomeric C-branched sugars show the influence of neighboring oxygenated groups as for the the preceding photosubstitutions at the anomeric positions. The importance of stereoelectronic effects seems predominant for all these radical reactions. 

In this publication the author describes the phenomenon that most times the thermodynamically less stable product (see 29) of the two possible rings (e.g. 5-exo and 6-endo) is formed. Today looking at the 5-exo cyclization it is known that, although the generated primary radical is less stable than a secondary one, stereoelectronic effects favor reaction to the kinetically controlled product. According to MO-calculations, for a successful cyclization, an angle of 70° of the incoming radical to the plane of the alkene-/alkyne-bond is necessary.11... 

The susceptibility to hydrogen abstraction of C-H bonds a to ethereal oxygen, which often reflects thermochemical, polar, and stereoelectronic effects, enables selective functionalization of ethereal a-C-H bonds [1, 2]. The resulting a-alkoxy-alkyl radicals stabilized by conjugative electron delocalization between the oxygen... 

Stereochemical data on reactions involving radicals substituted with one, two or three oxygen atoms at the radical centre is more extensive than data on the corresponding nitrogen species, and apparent stereoelectronic effects of around an order of magnitude in relative rates are known in a number of systems. A problem has been, however, that until recently the geometry of the radical intermediates has not been well defined. 

Further stereoelectronic effects on hydrogen abstraction reactions have been claimed by Malatesta and Ingold (1981) on the basis of their failure to observe the e.s.r. signal for the appropriate radical. Their necessary assumption, however, that rates of decomposition of product radical are the same as those of the reference radical is merely a pious hope. 

Generally, the reactions are carried out in refluxing benzene solution, since the yield in benzene is better than that in other solvents. Probably, the radicals formed may be somewhat stabilized by the weak orbital-orbital interaction between the radicals and benzene. However, from the environmental point of view, toluene or dioxane is recently used. As substrates, alkyl bromides or alkyl iodides are used, and the reactivity increases in the order prim-alkyl < seoalkyl < te/t-alkyl. Sugar anomeric bromide (3) is generally not so stable, so the reaction is carried out under irradiation conditions with a mercury lamp at room temperature (eqs. 4.2 and 4.3). There are two types of anomeric glycosyl radicals as shown in Figure 4.1. One is the axial radical [I], and the other is the equatorial radical [I ]. The axial radical is more nucleophilic than the equatorial radical due to the stereoelectronic effect, where this effect comes... 

A subsequent study ° from the Arnold group showed an intriguing stereoelectronic effect in oxidative benzylic carbon-hydrogen bond cleavage reactions of substrates 8 and 9 (Scheme 3.7). In this study, electron transfer reactions were conducted in the presence of a nonnucleophilic base. Radical cation formation also weakens benzylic carbon-hydrogen bonds, thereby enhancing their acidity. Deprotonation of benzylic hydrogens yields benzylic radicals that can be reduced by the radical anion of dicyanobenzene to form benzylic anions that will be protonated by solvent. This sequence of oxidation, deprotonation, reduction, and protonation provides a sequence by which epimerization can be effected at the benzylic center. In this study, tram isomer 10 showed no propensity to isomerize to cis isomer 11 (equation 1 in Scheme 3.7), but 11 readily converted to 10 (equation 2 in Scheme 3.7). The reactions were repeated in deuterated solvents to assure that these observations resulted from kinetic rather than thermodynamic factors. Trans isomer 9 showed no incorporation of deuterium (equation 3 in Scheme 3.7) whereas cis isomer 11 showed complete deuterium incorporation. The authors attributed this difference in reactivity to... 

Closs, G. L., Calcaterra, L. T., Green, N. J., Miller, J. R., and Penfield, K. W., 1986, Distance, Stereoelectronic Effects, and the Marcus Inverted Region in Intramolecular Electron-Transfer in Organic Radical-Anions J. Phys. Chem. 90 3673n3683. 

Gloss GL, Calcaterra LT, Green NJ, Penfield KW, Miller JR. (1986) Distance, stereoelectronic effects, and the Marcus inverted region in intramolecular electron transfer in organic radical anions. J Phys Chem 90 3673-3683. 

The dominant contributor to the reactivity of vinylcyclopropanes in any radical reaction is the form (4a), the cyclopropylcarbinyl radical system. The opening of a cyclopropylcarbinyl radical to a butenyl radical is among the fastest radical processes known, with a rate constant of 1.3 x 10 sec". - The various stereoelectronic effects of this rearrangement have been reviewed. The structure of (4a), deduced from its ESR spectrum - and in agreement with calculations (STO-36 basis set), is in the bisected conformation shown, predicted to be 1.4 kcal mol more stable than its perpendicularly oriented counterpart. Above -KX) T only the butenyl radical (4b) can be detected. Substituent efiects do not seem to operate here when the substituents are on the cyclopropane (i.e. product stabilization). The cy-clopropylcaibinyl cation and anion have structures similar to (4a), bisect conformations (5) and (6), respectively. A concise summary of solvolytic and mechanistic data for system (5) has recently appeai Reviews of cyclopropylcarbinyl anions and carbenes are also available. - ... 

Some tri- and tetracyclic alkanes contain two cyclopropane moieties locked into a fixed orientation. These arrangements might give rise to interesting stereoelectronic effects in the interaction between the cyclopropane rings. For example, CIDNP effects during electron-transfer reactions of syn- and a/jn -tricyclo[5.1.0.0 ]octane syn-, anfi-89) indicate significantly different structures for their radical cations. 

As discussed earlier, deprotonation of a-carbon forms a major reaction pathway for the disappearance of the amine radical cation. Studies of photoinduced electron-transfer reactions of tertiary amines by Lewis [7, 11] and by Mariano [5, 10] have contributed significantly towards our understanding of the factors that control this process. Lewis and coworkers used product-distribution ratios of stilbene-amine adducts to elucidate the stereoelectronic effects involved in the deprotonation process [5, 10, 121, 122]. In non-polar solvents, the singlet excited state of tran -stilbene forms non-reactive but fluorescent exciplexes with simple trialkylamines. Increasing solvent polarity brings about a decrease in the fluorescence intensity and an increase in adduct formation. For non-symmetrically substituted tertiary amines two types of stilbene-amine adduct can be formed, as is shown in Scheme 9, depending on whether the aminoalkyl radical adding to the stilbene radical is formed by de-... 

The rate of side-chain fragmentation of an alkylaromatic radical cation can be influenced by the relative orientation of the scissible bond and the aromatic n system (stereoelectronic effect). The orientation most suited for cleavage is that where the dihedral angle between the plane of the n system and the plane defined by the scissible bond and the atom of the n system to which this bond is connected is 90°. Scheme 27 shows the conformation most suited for C-H bond cleavage. 

As remarked previously, the deprotonation rate of an alkylaromatic radical cation can be influenced by the stereoelectronic effect (Scheme 27). In this respect, Tolbert provided convincing evidence for the operation of stereoelectronic effects in the deprotonation of 9-alkylanthracene and 9,10-dialkylanthracene radical cations... 

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