Nitroalkane anions

There exist a number of d -synthons, which are stabilized by the delocalization of the electron pair into orbitals of hetero atoms, although the nucleophilic centre remains at the carbon atom. From nitroalkanes anions may be formed in aqueous solutions (e.g. CHjNOj pK, = 10.2). Nitromethane and -ethane anions are particularly useful in synthesis. The cyanide anion is also a classical d -synthon (HCN pK = 9.1). 

Silylation of Products of Conjugated Addition of Nucleophiles to a-Nitroolefins Nitroalkane anions can be generated not only by deprotonation of nitroalkanes (various modifications of these process were considered above) but also by the conjugated addition of nucleophiles 56 to a-nitroalkenes (42) (Scheme 3.56, Table 3.2). 

Superoxide anion formed in situ in a solution exposed to air (i.e. with only a small concentration of O2) has been used as an EGB to generate nitroalkane anions that may add to activated alkenes or to carbonyl compounds [130, 131]. An example is shown in Scheme 33. The reaction is catalytic since the product anion can act as a base toward the nitroalkane. Using the nitroalkane as the solvent favors the proton transfer pathway over the competing addition of the product anion to a second molecule of activated alkene, a pathway that may lead to polymerization [130]. In some cases, better yields of the Michael addition product were obtained if a stoichiometric amount of the anion was formed ex situ (with O2 as the PB), and the activated alkene added subsequently ]130, 132]. 

The procedure described in Sect. 14.9.1 for addition of nitroalkane anions to activated alkenes can also be used for addition to aldehydes. The nitroalcohol formed can be dehydrated in almost quantitative yields in dilute H3PO4 in a subsequent step [130, 131]. Starting with... 

Let us follow the role of steric hindrance in a forming product during the course of process according to Komblum and Erickson (1981) as well as Akbulut et al. (1982). Scheme 6.5 clearly demonstrates the effect here, all of the constituent reactions were performed in equal conditions (HMPA as a solvent, at 25°C). The nature was proven for all the cases. The intermediary cumyl radical reacts with the nitroalkane anion, but this reaction is retarded with an increase in the size of an alkyl anion. The significance of the cumyl radical dimerization grows accordingly. 

Nitroalkanes are acidic compounds the dissociation of a proton from a nitroalkane produces the nitroalkane anion, or nitronate, whose chemical and physical properties differ from those of the parent nitroalkane. The nitronate form of 2-nitropropane is more mutagenic in S. typhimurium TAIOO and TA 102 than is the neutral parent compound (Fiala et al., 1987b Dayal et al., 1989 Kohl et al., 1994), suggesting that propane 2-nitronate may act as an intennediate in the mechanism by w hich 2-nitropropane exerts its genotoxic and carcinogenic effects. This hypothesis is supported by studies indicating that both bacterial mutagenicity and induction of unscheduled DNA synthesis in rat hepatocytes are decreased by conditions (low pH or deuteration of the secondary carbon atom) that limit formation of the nitronate tautomer, and that the tautomerization of 2-nitropropane can be influenced by hepatic enzymes (Kohl et al., 1994). 

One of the earliest applications of combined EPR and electrochemical measurements was the study of nitroalkane reductions [48]. Cyclic voltammetry revealed irreversible reduction waves, but some anodic peaks were observed on the reverse scan and were attributed to reaction intermediates. In situ generation produced an initial spectrum attributable to the nitroalkane anion radical, but after some time, the dialkylnitroxide spectrum was detected. This information, combined with analysis of the products formed during bulk electrolysis, suggested the following reaction sequence ... 

This anomeric stabilization of radicals is also observed using halonitrosugars such as 1-C-nitroglycosyl halides [22] 15. Captodative stabilization of the alcoxy nitro radicals explains the radical-chain substitution with mild nucleophiles such as ma-lonate or nitroalkane anions to form 16 (Scheme 8). 

Acylated 2-aminopyrazole 1-oxides 118 were prepared in excellent yields by heating (5-nitroacylhydrazones 117 to reflux with sodium methoxide in methanol (2006SL2731). The nitroacylhydrazones 117 were synthesized by treatment of 2-diaza-l,3-butadienes 115 with nitroalkanes 116 and catalytic amounts of sodium methoxide under solvent-free conditions at room temperature. The nitroalkane anion adds to the hydrazone 115 in a conjugated fashion producing diastereomeric mixtures of nitroac-ylhydrazone 117 in high yields (Scheme 36). 

Nitroalkane anions are very stable and hence excellent at conjugate addition (chapter 22). Quite weak bases such as amines are enough to give the anion of 44 and hence the nitro-ketones 45. Reduction gives the amino-ketones 46 that cyclise to give imines, reduced under the reaction conditions to pyrrolidines 47. 

Now comes the key step intramolecular conjugate addition of the nitroalkane anion to the unsaturated ester. When catalysed by CsF and a tetra-alkyl ammonium salt, this is selective (1.5 1) for the all equatorial products 100. Reduction and cyclisation give the lactam 102 having the right stereochemistry for (Llycorane 72. 

Equation 26. Electron-deficient flavins will also oxidize nitroalkane anions in model reactions (12). The observation (11) that nitromethane anion and FloXEt yield a stable 4a-adduct is evidence that 4a-adducts are not on the reaction path for nitroalkane oxidation. That the blocking of the N(5)-position of flavin (i.e., FloxEt) prevents oxidation of nitromethane would, however, be in accord with the requirement for an N(5)-adduct (11). The nitroalkane reaction with flavoenzyme has been used to implicate N(5)-adducts as intermediates in the oxidation mechanism of amino acid oxidases. However, it must be understood that nitroalkane anions differ significantly from the carbanions generated from a normal substrate. The nitroalkane anion on loss of its pair of electrons would provide an impossibly unstable carbonium ion, whereas in the case of the amino acid anion an internal electron release obviates carbonium ion formation. 

The nitroalkane anion cannot undergo a direct two-electron oxidation. However, once the nitroalkane N(5)-adduct is formed the internal displacement of the stable N02 species (Equation 26) should be favorable energetically. The imine species formed on loss of N02 from the condensation product of nitromethane and Flox is the same... 

In addition, the transfer of N-substituents from pyridinium cations to nitroalkane anions involves an electron-transfer mechanism not of the normal radical chain variety (83JA90). Further studies delineating the boundaries of competitive, distinct pathways in these reactions would be of general interest for better understanding of nucleophilic substitutions (86CJC1161,86JA7295 87ACR(ip)). 

Russell [67] recently reported the PET C—X bond cleavage reactions of a-substituted nitroalkanes, e.g. XC(CH3)2N02 with X = Cl, Br, N02) S02C6H5, SAr and N3, with alkoxide ions. The first step in the reaction is photostimulated ET from the alkoxide to the nitroalkane to produce a nitroalkane anion-radical which undergoes a C—X bond cleavage to produce a nitroalkane radical which reacts with alkoxide to provide a new anion-radical. The new alkoxynitro... 

Figure 5 Proposed carbanion mechanism for the reductive half-reaction of NAO. The lower path shows the off-pathway covalent adduct formed by attack of a second nitroalkane anion.

Srj I reactions can be initiated by photochemical excitation, electrochemical reduction, and solvated electrons (alkali metal in ammonia). In some cases, spontaneous thermal initiation can also take place. The leaving group, X , is often a halide—frequently bromide or iodide, never fluoride. The nucleophile, Y , is commonly a nitroalkane anion (5-25) or another anion such as thiolate (RS ), phenolate (PhO ), or various enolates. 

Anodic oxidation of the nitroalkane anion to a radical may lead to dimerization [22], addition to unsaturated systems [23], or substitution in aromatic compounds [24] these reaactions are treated in Chapter 22. 

Cleavage of C-N bonds has been described elsewhere, for example, the reduction of g wj-dinitroalkanes to nitrite ion and nitroalkane anion [181,182] and f-nitroalkanes to nitrite and alkyl radical (Chapter 9) and the reduction of pyridylamines to picoline and ammonia (Chapter 18) [13,14] a rare case of a reductive loss of a nitro group from a benzene ring in l,2,4,5-tetrafluoro-3,6-dinitrobenzene has been reported [183]. Reduction of activated azides yields azide ion phenacyl azide is thus reduced to acetophenone and azide [236]. 

The formation of a carbon-carbon bond by reaction of alkylthallium(III) compounds has been described in the a-nitroalkylation of alkanes. The reaction of alkylthallium (129) with nitroalkane anions leads to the nitroalkyl derivatives (130). In this case, radical intermediates generated by electron transfer activation of the carbon-thallium bond are involved in a non-chain substitution process. 

Mechanistically related are the reactions of nitroalkane anions with strongly electron-deficient olefins21"25. Following Michael addition, a cycloalkylation, under nitrite expulsion, produces cyclopropane derivatives with acceptor groups. At least in certain examples, the configuration of the precursor olefin is reflected in the stereochemistry of the resulting cyclopropane22. 

The S l reaction was first discovered and developed for nitroalkane anions, but it is applicable to several other types of nucleophiles. The S l reaction is applicable to various aryl and tertiary alkyl halides and has also been extended to other leaving groups. The reaction has found a number of synthetic applications, especially in substitution of aryl and bridgehead alkyl halides that are resistant to other substitution mechanisms. 

A number of papers deal with the N-NMR spectra of anions derived from mono- and polynitroalkanes. The change of structure from that of a true anion of aci-nitroalkane to that of a true nitrocarbanion was suggested in the series of anions of mono-, di-, and trinitroalkanes on the basis of the N spectra [SO]. Some data on the N, N, and resonance shifts were reported for nitroalkane anions [51—53] and O for nitroalkanes [54]. 

Carbon-carbon double bonds directly attached to indole rings have been shown to participate in cyclization reactions. The vinyl ether (395), on treatment with A -methylhydroxylamine, undergoes a 1,3-dipolar cycloaddition to the adduct (396) (Equation (110)) <85JA2569>. The intramolecular addition of a nitroalkane anion to an allylsulfinate gives a similar ergot alkaloid precursor (Equation (111)) <86TL3169>. 

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