Alkoxy radicals substituent effects

Bordwell compares the alkoxy effect with the C—H BDE for dimethyl ether as reported by McMillen and Golden (1982). The latter is lower by 12 kcal mol" than that of methane, and from the comparable magnitude of the effect in the a-alkoxy acetophenonyl radical it is concluded that an additive substituent effect exists. Similar arguments hold for the dimethylamino-substituted radical. It is stated that additivity is more than expected for bis-... 

Photooxetane formation is quite inefficient, a fact which usually points to the presence of an intermediate which can partially revert to ground state reactants. Cleavage of the diradical must be responsible for some of the inefficiency in oxetane formation 129>. However, in the past few years convincing evidence has appeared that a CT complex precedes the diradical iso.isi). The two most telling pieces of evidence are the relative reactivities of different alkenes 130> and the absence of any measurable secondary deuterium isotope effect on quenching rate constants 131>. Relative quenching rates of sterically un crowded olefins are proportional both to the ionization potentials of the donor olefins 130> and to the reduction potentials of the acceptor ketones 131>, as would be expected for a CT process. Inasmuch as n,n triplets resemble electron-deficient alkoxy radicals, such substituent effects would also be expected on direct radical addition of triplet ketone to olefin. However, radical addition would yield an inverse isotope effect (in, say, 2-butene-2,3-d2) and would be faster to 1,1-dialkylethylenes than to 1,2-dialkylethylenes, in contrast to the actual observations. 

Photocyclisation of 8-alkoxy-l,2,3,4-tetrahydro-l-naphthalenones and 4-alkoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones gives naphtho[l, 8-bc]furans and cyclohepta[cd]benzofurans respectively, and conformational and substituent effects of 1,5-biradicals in the cyclisation process are discussed." " The same authors also describe substituent effects on the photocyclisation of ethyl 2-(8-oxo-5,6,7,8-tetrahydro-l-naphthyloxy)acetates and ethyl 2-(5-oxo-6,7,8,9-tet-rahydro-5H-benzocyclohepten-4-yloxy)acetates to give naphtho[l,8-bc]furans and cyclohepta[c,d]benzofurans respectively." Also reported are cyclisations involving photogenerated radical cations of unsaturated silyl enol ethers, fragmentation cyclisations of unsaturated ot-cyclopropyl ketones which occur by photoelectron transfer and give polycyclics, and kinetic and theoretical studies of [2+3] cycloadditions of nitrile ylids. These reactions have been studied mechanistically and their synthetic potential investigated. 

The hyponitrites (16), esters of hyponitrous acid (HO N=N OH), are low temperature sources of alkoxy or acyloxy radicals. A detailed study of the effect of substituents on k4 for the hyponitrite esters has been reported by Quinga and Mendenhall,114... 

Investigation of replacement of the 5-methoxy group by substituents with different electronic and lipophilic properties and methylation of the indole nitrogen or its replacement by a sulfur atom was evidence for the shift of the 5-methoxy group to the 4-position of the indole nucleus led to the most active radical scavenger but much less effective as a cytoprotectant [135]. 5-alkoxy-2-(N-acylaminoethyl)indole (Fig. 15) appeared as the key feature to confer both antioxidant and cytoprotective activity to the structure. Antioxidant activity seems essential for cytoprotection, but it is not sufficient, and there is no statistically significant correlation between the two types of activity. 

Glycosides." The construction of p-glycosides has relied heavily on the anomeric effect (equatorial C2-acetoxy substituent). A recent approach relies on generation of a radical at an alkoxy-substituted anomeric position. The precursors (1) can be obtained as shown in equation (I). The same strategy can be applied to construction of (J-linked disaccharides. 

From substituent and solvent effects on reactions such as Eq. 20 it was concluded [84] that these reactions are of the SnI type, i.e. that alkoxyalkene (enol ether) type radical cations are intermediates. The lifetimes of these radical cations were estimated [84] to be of the order of nanoseconds, much shorter than those [78, 79, 81] of the corresponding l,l-radical cations. This shows the importance of the additional (second) alkoxy group in stabilizing the positive charge on the carbon skeleton. On the basis of these mechanistic model studies, very detailed suggestions could be made [84] regarding the deoxyribose-derived radical reactions that lead to chain breaks in DNA (see below). 

The electrolysis products of different carboxylates have been compared with the ionization potentials of the intermediate radicals. From this it appeared that alkyl radicals with gas-phase ionization potentials smaller than 8 eV mainly lead to carbenium ions. Accordingly, a-substituents such as carboxy, cyano or hydrogen support the radical pathway, whilst alkyl, cycloalkyl, chloro, bromo, amino, alkoxy, hydroxy, acyloxy or aryl more or less favor the route to carbenium ions. Besides electronic effects, the oxidation seems also to be influenced by steric factors. Bulky substituents diminish the extent of coupling. The main experimental factors that affect the yield in the Kolbe electrolysis are the current density, the pH of the electrolyte, ionic additives, the solvent and the anode material. 

Cyclopentyl radicals substituted in the /1-position relative to the radical center are formed during the solvomercuration/reductive alkylation reaction of cyclopentene34. The organomer-curial produced in the first solvomercuration step is reduced by sodium borohydride and yields free cyclopentyl radicals in a radical chain mechanism. Addition of alkenes can then occur tram or cis to the / -alkoxy substituent introduced during the solvomercuration step. The adduct radical is finally trapped by hydrogen transfer from mercury hydrides to yield the tram- and ris-addition products, The transicis ratio depends markedly on the alkene employed and it appears that the addition of less reactive alkenes occurs with higher trans selectivity. In reactions of highly substituted alkenes, this reactivity control is compensated for by steric effects. Therefore, only the fnms-addition product is observed in reactions of tetraethyl ethenetetracarboxylate. The choice of alcohol employed in the solvomercuration step has, however, only a small influence on the stereoselectivity. 

Heterocyclic cyclopentyl radicals formed in the solvomercuration/reductivc alkylation reaction of dihydrofuran give products with tram- selectivity in a slightly higher ratio than the corresponding carbocyclic analogs34. This is attributed to anomeric effects, which lead to a more pronounced axial orientation of the /J-alkoxy substituent in the tetrahydropyranyl radical. 

The ff-t5Tpe ethoxycarbonyl radical is on the contrary less nucleophilic than the acetyl radical (Table 29) in this Ccise the unpaired electron occupies a hybrid orbital and the incipient positive charge in the transition state cannot be stabilized by the lone-pair electron of the alkoxy group, as with the alkoxyalkyl radical, so that only the inductive effect is working and a clean reduction of nucleophilicity is observed. The remarkable fact is therefore that the same substituent, an a-alkoxy group, produces opposite polar effects depending on the electronic configuration of the carbon-centered radical. 

In many respects, the behaviour of amino and phenolic inhibitors can be predicted on the same grounds, because of the fact that the peroxy radical is an electron acceptor and prefers to react with a centre of high electron density [41]. As a result, electron-releasing substituents, such as alkoxy or alkyl groups, where they do not sterically hinder the reaction, will improve antioxidant performance. Bulky ortho substituents, which involve steric influences, may retard the rate of reaction [42], although this will obviously depend on individual systems. The effect of phenolic inhibitors has been dealt with elsewhere [1], but it is of interest to consider some factors that throw light on the mechanism and kinetics of amino inhibition. 

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