Aminyl generation

The attacking radical need not always be at carbon. Amidyl radical are known and give cyclization reactions. Aminyl radical cyclizations have been reported. Oxygen radical can be generated under photochemical conditions, and they add to alkenes in a normal manner. ... 

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]. 

New cyclizations via photochemically generated aminyl radicals have been reported, including further examples of the Hofmann-Loeffler-Freytag reaction.313 Intramolecular addition of an aminyl radical, generated by photochemically induced nitrogen chlorine bond homoysis, is also accompanied by cyclization as illustrated by the conversion of the unsaturated N-chloroamide 378 to the pyrrolidine 379.314 Piperidine formation can also... 

Cyclic acetals. In combination with iodine, this reagent resembles lead tetraacetate in the ability to generate alkoxy or aminyl radicals (12,243) under thermal or light activation. This radical oxidation can be used to convert p- or y-hydroxy ethers into dioxolanes or dioxanes.4... 

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

A general method for the generation of aminyl radicals is by treatment of sulphenamides 340, prepared from secondary amines and A-benzenesulphenylphthalimide, with tributyltin hydride in the presence of AIBN (2,2/-azobisisobutyronitrile). The cyclopropyl derivative... 

Neutral aminyl radicals generated by anodic oxidation of lithium alkenyl amides undergo a stereoselective cyclization to cis-l-methyl-2,5-disubstituted pyrrolidines [249]. 

A similar procedure has successfiiUy generated aminyl radicals by treating the iV-carbamates of Ar-hydroxyl-2-thiopyridones (40) with radical initiators such as RS- and RsSi-. The aminyl radical generated abstracts a proton or adds intramolecularly to the double bond to result in the cycli-zation products shown in Scheme 26 (87JA3163). 

Dihydro-l, 2,3,5-thiatriazole 1-oxide radicals were generated from the thiatriazole oxides upon hydrogen abstraction in the reaction with thermally formed bis(4-methylphenyl)aminyl (4.20.5.1). Only radicals with aryl substituents in positions two and four are persistent, radicals with alkyl groups in these positions could not be detected. The radicals were investigated by ESR, ENDOR, and general triple resonance spectroscopy <92MRC84>. 

Inhibition mechanisms by A/-cyclopropyl MPTP analogues are also discussed in terms of two catalytic pathways, one of which is based on an initial SET step from the nitrogen lone pair, as proposed by Silverman, and the second is based on an initial a-carbon hydrogen atom transfer (HAT) step, as proposed by Edmondson, leading to a radical and dihydropyridinium product formation. The observation that MAO B catalyzes the efficient oxidation of certain 1-cyclopropyl-4-substituted-1,2,3,6-tetrahydropyridines to the corresponding dihydropyridinium metabolites suggests that the catalytic pathway for these cyclic tertiary allylamines may not proceed via the putative SET-generated aminyl radical cations [122], Further studies will be necessary to clarify all the facets of the mechanism of inhibition of MAO by cyclopropylamines. 

The rate constant of this reaction was measured by flash photolysis with tetraphenyl-hydrazine as a source of diphenylaminyl radicals [64]. Peroxyl radicals were generated through the photodecay of bis(l,l-dimethylethyl) peroxide followed by the rapid reaction of formed alkoxyl radicals with cyclohexane used as a solvent the reaction conditions were chosen in such a way that [R02 ]o > [Ph2N ]0. Under these conditions, aminyl radicals were destroyed only in the reaction with peroxyl radicals and, hence, the concentration of peroxyl radicals during the measurement of the kinetics of Ph2N consumption varied insignificantly. The rate constant of the recombination of peroxyl and diphenylamine radicals was found to be equal to 6 x 108 L mol 1 s 1 (cyclohexane, 283-303 K). 

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))... 

Epimines. Irradiation of nitroamines and cyanoamines in the presence of phenyliodine(III) diacetate and iodine generates an aminyl radical which undergoes intramolecular hydrogen abstraction to produce epimines. 

Aminyl radicals can also be generated from amide bases and organic oxidants via an electron transfer process. The utility of /V-lithio-Af-butyl-5-methyl-l-hex-4-enamine (10) as a mechanistic probe for such a process was studied (Scheme 2) (88JA6528). The formation of cyclic pyrrolidine... 

Aminyl radicals also can be generated via electrochemical oxidation of amide bases or O-substituted hydroxylamines. Suginome has studied radical cyclizations involving oxidations of lithium alkenylamides as a route to ccs-l-methyl-2,5-disubstituted pyrrolidines (85TL6085). Electrolysis of lithium alkenylamide 17a, generated from the amine and butyllithium at - 78°C, led to the formation of 18a, exclusively cis, in 52% yield (Scheme 4). The reactions require 0.25 M UC104 in THF HMPA (30 1) as the supporting electrolyte. A variety of 2-substituted amines were studied. 

Cyclization of electrochemically generated aminyl radicals is more efficient when the species contains a phenyl-substituted double bond. Evidently, this facilitates cyclization relative to other reactions, and good yields of 5-unsubstituted, 5-alkyl, and 5-aryl-2-benzylpyrrolidines were obtained (Table II, entries 4-6) (91T747). Moderate yields of 4-substituted-2-benzylpyrrolidines also were obtained (entries 7-8). Again, the stereoselectivity was excellent for R2 = Ph, but it was only 3 1 for R2 = CHV... 

The use of /V-chloramines, in principle, allows the facile generation of aminyl radicals upon UV photolysis in neutral media. A radical chain can be envisioned for the formation of 2-chIoromethylpyrrolidines (Scheme 7). In practice, however, there is a slow step in this sequence, step A and/or B, such that other reaction pathways, disproportionation or H-abstraction from the solvent, compete. Surzur has studied the reaction in Scheme 7 in the alcoholic solvents MeOH and /-PrOH, which serve as hydrogen atom sources, and achieved acceptable ratios of cyclic products 25 and 26 to acyclic amine 27 (70TL3107). Other /V-chloroalkenylamines gave similar results (71TL903 80TL287). /8-chloro-substituted amine products such as 25 were the sole products when the reactions were carried out in acetic acid-water mixtures these reactions involve aminium cation radicals and are discussed further in Section III,B. 

The mechanism of aminyl radical generation from PTOC carbamates follows closely the radical chain mechanism of alkyl radical generation from PTOC esters. The chain reaction sequence involves the series of steps shown in Scheme 8. Several methods for inducing N —O bond cleavage are possible. Photochemical decomposition of 29 via visible light irradiation is used to initiate the chain reaction sequence at ambient or subambient temperature reactions have been run as low as -78°C (91TL6493). 

The PTOC carbamate method for efficient and controlled generation of aminyl radicals allows kinetic studies that previously were not possible with tetrazene precursors. As is the case with carbon radicals, optimum synthetic utility of chain reaction sequences is found when absolute rate constants or ratios of rate constants for competing reactions are known, i.e., Scheme 8, step D vs step E. If an absolute rate constant is known for one reaction, then other absolute rate constants can be determined for other reactions from the product distributions in competitions of the reactions of interest with the reaction with a known rate constant. 

Aminyl radicals can be protonated with Br0nsted acids or complexed by Lewis acids to generate an electrophilic nitrogen radical. The pKa of an aminium cation radical in water is =7 as determined from a titrametric... 

Electrophilic radical cyclizations of alkenyl aminium cation radicals have shown synthetic utility. Hofmann-Loffler-Freytag reactions do not compete with 5-exo cyclizations (75BSF1429). The homolytic cyclization of Af-chloroalkenylamines under acidic or Lewis acidic conditions has been studied primarily by Surzur and Stella, and the chemistry of these precursors for electrophilic aminyl radical generation has been reviewed [83AG(E)337]. Radical chain reactions can be initiated by heat, UV photol-... 

One of the best methods for the controlled generation of alkenaminyl radicals is via PTOC carbamates (Section II,E). These precursors react in efficient radical chain reactions with hydrogen atom donors to form amines and pyrrolidines. They are stable to anhydrous acids and, therefore, are suitable precursors for aminium radicals produced by protonation of the first-formed neutral aminyl radical. 

Neutral aminyl radicals generated from tin hydride-mediated reactions of sulfenamides (Section II,F) have been shown to undergo cyclizations when energetically favored by addition to a strained alkene or by formation of a stabilized intermediate benzylic radical. In both cases, the reverse reaction, cleavage of the /3-amino radical, apparently did not occur (92TL4993). 

---