Radical a-oxyalkyl

Hydrogen abstraction from a position a to the oxygen of alcohols and ethers provides a simple route to a-oxyalkyl radicals. Resonance stabilization and polar factors have been used to explain the ease of radical attack on these substrates. Recent studies appear to exclude the possibility that the oxygen atom in position a to the free C-radical may cause stabilization by resonance. The ease of hydrogen abstraction Avould be determined only by polar factors, arising with electrophilic radicals (X ) in contributions from the polar forms 13-15 to the transition state. 

The a-oxyalkyl radicals used for alkylating heteroaromatic bases are formed by the oxidation of alcohols and ethers with a variety of electrophilic radicals or photochemically. 

Acyclic ethers undergo partial j8-scission with formation of carbonyl and alkyl derivatives. Thus with ethyl ether the introduction of the oxyalkyl group is accompanied by appreciable quantities of ethyl and acetyl derivatives, attributed to jS-scission of the a-oxyalkyl radical [Eq. (47)]. 

Oxidative decarboxylation of a-oxy carboxylic acids is another general route for a-oxyalkyl radicals [Eq. (16)]... 

Carbamoyl and a-N-amidoalkyl radicals can be easily obtained by hydrogen abstraction from formamides and N-alkylamides. They have a close analogy with acyl and a-oxyalkyl radicals. The nucleophilic character of the carbamoyl radical is explained by the fact that it can be considered an acyl radical in which the alkyl or aryl group is substituted by an amino group it can be related with resonance structures like 16... 

Ab initio calculations of Giese [17] and Houk [18] have demonstrated that the geometry of the H-abstraction reaction by a-oxyalkyl radicals 46 resembles that of a nucleophilic addition to a carbonyl group 47. 

Along with tin hydride-mediated arylations, electrochemical [61], photochemical [62] and iodine transfer methods [63] have each been successfully used for the generation of alkyl radicals in homolyhc aromahc subshtuhons. Moreover, nucleophilic a-oxyalkyl radicals, prepared from the corresponding aldehydes by treatment with either samarium diiodide [64] or stannyl radicals [65], reacted with arenes to afford the homolyhc subshtuhon products. In a series of reports, Zard highlighted the potenhal of xanthates as alkyl radical precursors in homolytic aromatic subshtuhons [66]. 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

Oxidation of alcohols with a variety of oxidizing agents leads to a-hydroxyalkyl radicals. These attack protonated heteroaromatic bases only when obtained from methanol or primary alcohols, with secondary alcohols no attack takes place, probably owing to the ease with which such a-hydroxyalkyl radicals are oxidized. (This limitation does not apply to radiation-induced oxyalkylation, see later.)... 

The presence of a long oxyalkyl radical R" appeared to protect the molecule from degradation ... 

Recently, it has been demonstrated by Sweeney and co-workers that fi-lactones can also be prepared by radical 4-exo cychsation methodology [93], The intermediate 0-(alkenoyl)oxyalkyl radicals 101 could be prepared by tin hydride treatment of the corresponding (l-bromopropyl)cinnamate. However, best results were obtained with N-hydroxypyridine thione (PTOC) esters 100. In this case a toluene solution of the PTOC ester and BusSnH was slowly added by syringe pump to a heated flask irradiated with a timgsten lamp (Scheme 22). For precursors containing only one substituent at the terminus of the double bond the direct reduction was the main process. For precursors 100 with two phenyl or two arylthio substituents, 4-exo cyclisation of the intermediate C-centred radicals 101 was efficient and good yields of -lactones 103 were isolated, accompanied in each case by minor amounts of the direct reduction product. The bis-arylthio functionahty was particularly appropriate for further FGI. 

Buratti, W., Gardini, G. P., Minisci, F., Bertini, F., Galli, R., Perchinunno, M. Nucleophilic character of alkyl radicals. V. Selective homolytic a-oxyalkylation of heteroaromatic bases. Tetrahedron 1971, 27, 3655-3668. 

A different approach involves the intramolecular pinacol coupling of 1,5- or 1,6-dialdehydes or -ketoaldehydes with a tin hydride. The ring is closed by an Sh2 reaction of the oxyalkyl radical at the tin centre.68... 

It is interesting to see that the classical experiments of Cram with ketone 53a-c and LiAlH4 have a radical counterpart with (Me3Si)3SiH as reagent, which leads to oxyalkyl radicals 56 as intermediates (Scheme 11). 

In the course of the polymerization of monomer lb with maleic anhydride, oxyalkyl radicals on the furanosyl rings were formed, as they were more stable than alkyl radicals as shown in Scheme 4. The addition of maldc anhydrides on the radicals could lead to a- or P-... 

Alkylation and arylation. The homolytic a-oxyalkylation of heteroaromatic bases using alcohols and ethers as radical sources has been studied. Although detailed experiments were chiefly concerned with quinoline and quinoxaline, benzothiazole was shown to yield 2-dioxanylbenzothiazole (40%) under the standard conditions. ... 

Here we show a novel methodology for the functionalizations of hydrocarbons, including oxygenation, nitration, sulfoxidation, epoxidation, carboxylation, and oxyalkylation through generation of the catalytic carbon radical. In particular, the NHPI-catalyzed aerobic oxidations of alkanes, which are very important in industry worldwide, are described in detail. 

Conjugated a-sexithiophenes show differences in electrochemical behavior, although the electronic inductive effects of these substituents are comparable. Long alkyl or oxyalkyl side chains lead to an enhancement of electrochemical reversibility and stabilization of the cation radical state [501]. 

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