Imine radical anions

The carbon-nitrogen double bond in imines is reduced at less negative potentials than the corresponding carbonyl function. Also imine radical-anions are more basic than carbonyl radical-anions. Imines with at least one phenyl substituent on the carbon-nitrogen double bond are sufficiently stable for examination in aprotic solvents and reversible one-electron reduction of benzaldehyde anil [179] or benzophenone anil [ISO] can be demonstrated with rigorous exclusion of moisture. 

Because they are isoelectronic, it is reasonable to expect that imine radical anions (>C=N— ) would exhibit chemistry analogous to that of >C=0. Such does appear to be the case, based upon the limited information available. 

Imine radical anions appear to be substantially more basic than their ketyl anion counterparts. In 1991, Zhan and Hawley reported that Ph2C=NH (generated via the electrochemical reduction of benzophenone imine) was a sufficiently strong base to depro-tonate weak carbon acids whose pK values were as high as 33185. 

C-C bond formation in inter- or intramolecular additions starting with olefin [ 199, 200], ketyl [201] (generated by PET [202], chemical or cathodic [24, 203] reduction) [204, 205] or imine radical anions [206] has become a versatile method. In general, the intramolecular addition is highly suitable for the construction of five membered rings, less so for six-, and not effective for seven-membered ring formation. 

SET with A -sulfonyl aldimine to form imine radical anion. In the presence of chiral ionic Bronsted acid catalyst, the resulting A -sulfonyl aldimine radical anion prefers to form a chiral ion pair. The radical-radical heterocoupling of a-aminoalkyl radical with chiral ion pair-based anion radical affords 1,2-diamine derivatives in high enantioselectivties. 

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... 

The ready protonation of radical anions under conditions of proton availability causes other problems to appear, as for example shown by the stepwise cathodic reduction of PBN to the corresponding imine and amine [reactions (59) and (60)] during which the intermediate radicals [21] and [22] appear and become trapped by PBN (Simonet et al., 1990). 

The aza-di-TT-methane (ADPM) rearrangement of aza-1,4-dienes via radical-cat-ions suggests the possibility that other radical-ion intermediates (e.g., radical-anions) could also be responsible for this rearrangement reaction. In order to test this proposal, the azadiene 101 was irradiated for 20 min in acetonitrile using A,iV-dimethylaniline (DMA) as an electron-donor sensitizer. The reaction leads to formation of the cyclopropylimine 102. Separation of product mixture by column chromatography on silica gel affords the aldehyde 34 (21%) resulting from hydrolysis of the imine 102, (Scheme 18) [70]. 

Electron transfer reduction of pyridines in both acid and alkaline solution generates the protonated radical-anion. This rapidly accepts a further electron and a proton to give a mixture of dihydropyridines. Enamine structures in these dihydro-pyridines can tautomerise to the imine, which is more readily reduced than the original pyridine molecule. Further reaction of the 1,4-dihydropyridine leads to piperidine while reduction of the t, 2-dihydropyridine leads to a tetrahydropyridine in which the alkene group cannot tautomerise to the imine and which is not therefore reduced to the piperidine stage. The reaction sequence is illustrated for 2,6-dimethyl-pyridine 18 which yields the thermodynamically favoured cis-2,6-dimethylpiperidine in which the two alkyl substituents occupy equatorial conformations. 

Under ordinary conditions, reduction of these imines in dimethylformamide is a two-electron process involving saturation of the carbon-nitrogen double bond [181] because the radical from protonation of the radical-anion is more easily reduced than the starting imine. Immonium salts with two or more phenyl substituents are reduced reversibly in acetonitrile to the radical-zwitterion such as 42. Other immo-niura salts, e.g. 43, are reduced irreversibly to the dimer [182]. Radical-zwitterion intermediates generated from immonium salts exhibit nucleophilic character on carbon. Intramolecular interaction between the reduced immonium function and a... 

The radical-anion intermediates derived from aromatic imines behave as nucleophiles towards carbon dioxide, as with 48 [190,191]. Ibis nudeophic character is enhanced by reduction in the presence of chlorotrimethylsilane. A carbanion... 

Quinone Imines. - These display similar chemical properties to quinones, differing slightly due to the difference in electronegativity between the -C = O and -C=NH functions. Alberti et al. have examined the redox properties of the anti-cancer agent 5//-pyridophenoxazin-5-one. 18 Electrochemical reduction under anaerobic conditions gave the spectrum of the radical anion 02 was trapped in the presence of 02. 

A quaternary ammonium salt Et N+ p-TsO" can be changed to a melt at 120°C. More than 30 years ago, Weinberg successfully used this melt for electrochemical synthesis of an a-amino acid derivative from an imine and CO2 using a mercury cathode, as shown in Scheme 8.15 [41]. The reaction proceeds via the radical anionic intermediate of the imine. 

Reduced acceptor substrates such as n radical anions can form complexes with neutral or cationic metal species which may be quite persistent, especially if the acceptors contain good metal coordination sites such as carbonyl oxygen or imine nitrogen groups (3,8) [14,78]. 

The reduction of imines to amines (equation 21) by dissolving metals is usually carried out using active metals in a protic solvent, typically Na-alcohol, Zn-NaOH and A1 or Mg in alcohols. - ""- Although the mechanism of these reductions has not been investigated in detail it is almost certainly analogous to that of the reduction of ketones (Section 1.4.2). It has been established that radical anions are intermediates in these reductions and in the absence of a proton donor reductive dimerization is the principal reaction path. ... 

In imine reductions rapid equilibration of dimeric dianions and the precursor radical anions leads to the thermodynamically more stable isomer [257]. In the reductive coupling of salicylideneanilines, however, rate-determining C-C bond formation is preceded by intramolecular H-bridging [258]. 

Photoreduction of benzophenone by primary and secondary amines leads to the formation of benzpinacol and imines [145]. Quantum yields greater than unity for reduction of benzophenone indicated that the a-aminoalkyl radical could further reduce the ground state of benzophenone. Bhattacharyya and Das confirmed this in a laser-flash photolysis study of the benzophenone-triethylamine system, which showed that ketyl radical anion formation occurs by a fast and a slow process wherein the slow process corresponds to the reaction of a-aminoalkyl radical in the ground state of benzophenone [148]. Direct evidence for similar secondary reduction of benzil [149] and naphthalimides [150] by the a-aminoalkyl radical have also been reported. The secondary dark reaction of a-aminoalkyl radicals in photo-induced electron-transfer reactions with a variety of quinones, dyes, and metal complexes has been studied by Whitten and coworkers [151]. 

Radical anions of carbonyl groups and imines also seem to be produced in the presence of titanium (IV) chloride in methanol as solvent. Consecutive oxidation and deprotonation of methanol leads to hydroxymethyl radicals which combine with the carbonyl radical anions to give 1,2-diols and 1,2-aminoalcohols, respectively. The synthesis of the pheromone frontalin has been achieved in a one-pot reaction by hydroxy-methylation of a diketone [127-129]. Likewise triplet sensitizers [130] can be used for direct excitation of the substrate in methanol [131]. Chiral aldimines can be conveniently hydroxymethylated with moderate diastereoselectivity by irradiation of methanolic solutions in the presence of an excess TiCU (Scheme 34) [132]. 

In MeCN, most Schiff bases give a single two-electron wave the radical anions of imines are more basic than the corresponding ketyl anions and are able to abstract a proton from the medium [24]. Aliphatic ketimines behave similarly in dimethylformamide (DMF) [23], whereas some aldehyde anils give two peaks in cyclic voltammetry (CV), depending on the... 

Lithiations of A-substituted perimidines so far have been restricted to the A-methyl derivative, which was found to undergo preferential addition across the imine double bond with alkyllithiums, and radical anion formation with LDA <88AJCI39>. Some C2 lithiation does occur, however, as indicated by the formation of an 8% yield of the 2-carboxylic acid after reaction with -BuLi and carbon dioxide (siRCRSie), and a 19% yield of bis(2-perimidinyl)carbinol after treatment with LDA and DMF <88AJC139>. 

Unfortunately, ( PDI)Mn(THF)2 exhibited little activity for the hydrogenation of alkenes or [2 + 2] cyclization of dienes. In an attempt to synthesize an active bis(imino)pyridine manganese precatalyst, alternative reduction conditions were explored. Sodium amalgam reduction of ( PDI)MnCl2 in pentane yielded the red bis(chelate) complex ( PDI)2Mn. X-ray diffraction established a cis-divacant octahedral compound where one imine arm on each of the chelates is dissociated from the metal center. The metrical parameters from X-ray diffraction in conjunction with SQUID magnetic and EPR spectroscopic data established that the overall S = 3/2 compound is best described as a high-spin Mn(II) species (Sy = 5/2) with two bis(imino)pyridine radical anions. 

The mechanism of the Gibbs reaction, an assay for phenols using, e.g., 2,6-dichlorobenzoquinone iV-chloroimine, has been probed for a wide range of imines and phenols. The first step of single-electron transfer to produce the iV-chloroimine radical anion is followed by a mechanistic divergence into three routes, depending on the reactivity of the pair of reactants. 

Aldehydes and ketones are useM building blocks in organic synthesis. The direct a-C-H substitutions of carbonyl compounds are well known. However, selective P-C(sp )-H functionalization remains rare. The MacMillan group introduced Site activation model by dual aminocatalysis and photocatalysis, opening up a practical synthetic route to P-substituted aldehydes and ketones (Scheme 3.25). With this novel strategy, radical-radical coupling of enaminyl radical with electron-poor cyanobenzene radical anion can elegantly produce P-aiylated aldehydes and ketones [74]. A recombination of enaminyl radical with imine anion radical was also developed [75]. In the presence of Michael acceptors, radical addition of enaminyl radical to electron-deficient alkenes affords P-alkylated aldehydes [76]. 

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