Reductive aminyl radical

The reductive couphng of imines can follow different pathways, depending on the nature of the one-electron reducing agent (cathode, metal, low-valent metal salt), the presence of a protic or electrophihc reagent, and the experimental conditions (Scheme 2). Starting from the imine 7, the one-electron reduction is facihtated by the preliminary formation of the iminiiim ion 8 by protonation or reaction with an electrophile, e.g., trimethylsilyl (TMS) chloride. Alternatively, the radical anion 9 is first formed by direct reduction of the imine 7, followed by protonation or reaction with the electrophile, so giving the same intermediate a-amino radical 10. The 1,2-diamine 11 can be formed from the radical 10 by dimerization (and subsequent removal of the electrophile) or addition to the iminium ion 8, followed by one-electron reduction of the so formed aminyl radical. In certain cases/conditions the radical 9 can be further reduced to the carbanion 12, which then attacks the... 

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

In the presence of dissolved dioxygen, the hydroxyalkyl radicals are converted into the hydroxyperoxyl radicals very rapidly therefore, only hydroperoxyl and hydroxyalkylperoxyl radicals participate in the reduction of the aminyl radicals. The higher the temperature, the more effective the decomposition of the hydroxyperoxyl radicals and the higher the proportion of the H02 radicals participating in the regeneration of the amine. 

A review of the generation of aminyl radicals by photolysis and by metal-induced one-electron reductions of TV-chloroamines has appeared379. 

The reductive cleavage of hydroxylamine and its derivatives by electro-generated TP and V forming aminyl radicals and the hydroxide ions has been studied intensively. The aminyl radicals are preferably trapped with alkenes and aromatic compounds. Thus, the reaction of hydroxylamine with electro-generated Tp in the presence of maleic acid yields aspartic acid (Eqs. (66)—(69))... 

An amidyl radical is intermediate in reactivity between a neutral aminyl and an aminium cation radical due to the electron withdrawing ability of the carbonyl group. An intuitive advantage of amidyl radicals over aminium cation radicals is that reactions can be carried out under strictly neutral conditions, and, by reduction or hydrolysis of the amide, amidyl radical reactions become equivalent to reactions of neutral dialkyl or monoalkyl aminyl radicals. Preparation of AMraloamides and their rearrangements have been reviewed (71S1). 

Marcus treatment does not exclude a radical pathway in lithium dialkyl-amide reduction of benzophenone. It does, however, seem to be excluded (Newcomb and Burchill 1984a,b) by observations on the reductions of benzophenone by N-lithio-N-butyl-5-methyl-l-hex-4-enamine in THF containing HMPA. Benzophenone is reduced to diphenylmethanol in good yield, and the amine yields a mixture of the acyclic imines no cyclic amines, expected from radical cyclization of a putative aminyl radical, were detected. An alternative scheme (17) shown for the lithium diethylamide reduction, accounts for rapid formation of diphenylmethoxide, and for formation of benzophenone ketyl under these conditions. Its key features are retention of the fast hydride transfer, presumably via the six-centre cyclic array, for the formation of diphenylmethoxide (Kowaski et al., 1978) and the slow deprotonation of lithium benzhydrolate to a dianion which disproportion-ates rapidly with benzophenone yielding the ketyl. The mechanism demands that rates for ketyl formation are twice that for deprotonation of the lithium diphenylmethoxide, and, within experimental uncertainty, this is the case. 

Carbonate and carbamate derivatives, prepared from the reaction of alcohols and amines with phosgene and /V-hydroxy-2-thiopyridone, provide the corresponding alkoxyl radicals and aminyl radicals respectively, via radical decarboxylation [71-81]. For example, photolytic treatment of carbamate (57) derived from 4-pentenylamine generates the corresponding 4-pentenylaminyl radical, as shown in eq. 8.24. Under neutral conditions in the presence of tert-BuSH, a direct reduction product (A) of 4-pentenylaminyl radical is formed, while, in acidic conditions, cyclized product (C), pyrrolidine, via 5-exo-trig manner from 4-pentenylaminyl radical is formed. Under the latter conditions, the real reactive species is an electrophilic 4-pentenylaminium radical which rapidly cyclized via 5-exo-trig manner. 

Isoxazolines are related to 1,2-dioxines in that they are also prone to reductive ring opening. Ishikawa and colleagues found that A-benzylisoxazolines form 2-acylaziridines by SET reduction/ring opening and recyclization of the resulting aminyl radical to the cobalt enolate [430]. 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

Again, no reaction was observed in the absence of mercaptoethanol. The mechanistic steps for the transformation were elucidated by the Chatgilialoglu et ah and are represented in Scheme 4.13, in analogy with the pathway reported for the radical reduction of aromatic azides with triethylsilane in toluene, with the addition of silyl radicals to the azide function, liberation of nitrogen and formation of silyl-substituted aminyl radical. The thiol is the hydrogen atom donor to this intermediate and it can be regenerated by its interaction with the silane, thus propagating the chain. The hydrolysis of the silylamine occurred... 

Each aromatic amine molecule, InH, terminates many free radical chains in autooxidation of alcohols and amines due to the ability of oxyperoxy and aminoperoxy radicals to oxidize InH as well as to reduce In to InH (JO. However, the coefficient of inhibition, f > 2, can be very often observed in oxidizing hydrocarbons too (2 ). Therefore, some reduction of aminyl radicals to InH proceeds in oxidizing hydrocarbons. To ellucidate the ways of such reduction we have studied the products and kinetics of the reactions of diphenylaminyl radical In. ... 

Aminyl radicals are less reactive than carbon radicals, which in turn are less reactive than alkoxy radicals. For dialkylaminyl radicals, the reduction rate constant with tributyltin hydride 5 x 10 M s ) [14] is about ten times lower than for primary alkyl radicals [15] and a thousand times lower than for alkoxy radicals [16]. 

Polycyclization processes involving aminyl radicals have been described by Surzur and Stella. The aminyl radical 437 (Scheme 153) generated by Ti(III) reduction of the corresponding AT-chloroamine gives the iV-chloromethyl-pyrrolizidine 440 as only product, in 66% yield by two consecutive (Cy 5) cyclizations (Cy5/Cy6 cases).Cuprous halide initiation gives only monocyclic compounds by fast ligand transfer to 438 this has been used as an argument for a radical chain mechanism in titanous initiated cyclization of unsaturated 7V-chloroamines (see Section VIII.3.A, Scheme 42). 

However, under suitable conditions, azides react with a variety of radicals and this is the basis of several useful synthetic procedures for the formation of carbon-nitrogen bonds. For instance, synthesis of azides by radical addition of an azidyl radical to alkenes (Scheme 8.3a) and by reaction of an alkyl radical with an azidating reagent (Scheme 8.3b) will be presented. The reduction of azides leading to aminyl radicals (Scheme 8.3c) and the addition of alkyl radicals to alkyl azides (Scheme 8.3d) will also be discussed. 

The reduction of alkylazides by single electron transfer (SET) cleanly furnishes the alkyl-aminyl radicals plus molecular nitrogen. A variety of metal reagents and photochemical methods exist. The reaction can also be performed with organic radicals, which add to the azide and release dinitrogen, too (see also Section 8.3.2). The resulting aminyl radical can be simply reduced to the corresponding amine or can further react with radical traps (olefins) to form C-N bonds. 

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