Nitronate anions

Reaction of 2-chloromethyl-4//-pyrido[l,2-u]pyrimidine-4-one 162 with various nitronate anions (4 equiv) under phase-transfer conditions with BU4NOH in H2O and CH2CI2 under photo-stimulation gave 2-ethylenic derivatives 164 (01H(55)535). These alkenes 164 were formed by single electron transfer C-alkylation and base-promoted HNO2 elimination from 163. When the ethylenic derivative 164 (R = R ) was unsymmetrical, only the E isomer was isolated. Compound 162 was treated with S-nucleophiles (sodium salt of benzyl mercaptan and benzenesulfinic acid) and the lithium salt of 4-hydroxycoumarin to give compounds 165-167, respectively. 

Various side-reactions may complicate the course of the Nef reaction. Because of the delocalized negative charge, the nitronate anion 2 can react at various positions with an electrophile addition of a proton at the a-carbon reconstitutes the starting nitro alkane. 1. The nitrite anion can act as leaving group, thus leading to elimination products. 

Method B In contrast, reprotonadon of the rfirr-bntyldimethylsilyl-protected nitronate anions gives ruiri-isomets selecdvely... 

Carbon alkyUdon of simple nitronate anions is aiso possible by the reaction with iV-snbsd-tiited pyridiruums, as exemplified in Eq. 5.41. Such types of reacdons are classified as Spj 2 reacdons, in which electron transfer reacdons from nitronate anions to pyridiruums are involved as key steps." ... 

Anodic oxidation of nitronate anions provides an artracdvemethod for theNef reaction fEq. 

Michael addition of alkyl organometallic reagents to a,/ -disubstituted nitroalkenes followed by protonation of the intermediate nitronate anion generally gives mixtures of syn- and anti-diastereomers with poor diastereoselectivity19. 

The initial nitronate anion intermediates formed from the addition of trimethylaluminum to nitroalkenes having a /i-phenylthio substituent, however, undergo a highly diastereoselective protonation to give awn -products19. 

While a different explanation for the diastereoselection in these protonation reactions has been proposed, the stereochemical sense of protonation can be rationalized as arising from protonation of the chelated intermediate from the least hindered diastereotopic face of the nitronate anion (i.e. anti to the /i-methyl group)20-21. 

The precipitate that forms during ozonolysis sometimes impedes stirring, and in some cases it may be necessary to dilute the slurry with another 100 ml. of methanol after the first hour. Solid can also clog the gas-dispersion tube. The submitters scraped the fritted-glass tip occasionally to maintain a constant flow rate, whereas the checkers prepared a more dilute solution of nitronate anion (Note 3). 

J. E. McMurry, J. Melton, and H. Padgett, J. Org. Chem., 39, 259 (1974). We have recently been informed that ozonoly3is of nitronate anions was first reported in a paper by F. Asinger, Ber77, 73 (1944). 

In the case of nitronates possessing ester or nitrile moieties as terminal olefin substituents, tandem Michael addition to produce substituted furans 174,175 occurred faster than trapping of the nitronate anion by TMSCl (Eq. 17). 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

The nitro group can be converted to a ketone by hydrolysis of the nitronate anion, permitting the synthesis of 1,4-dicarbonyl compounds. 

In general, the Henry reaction proceeds in a non-selective way to give a mixture of anti (erythro) and syn (threo) isomers. Ab initio calculations on the Henry reaction suggest that free nitronate anions (not influenced by cations) react with aldehydes via transition states in which the nitro and carbonyl dipoles are antiperiplanar to each other. This kind of reaction yields anti-nitro alcohols. The Henry reaction between lithium nitronates and aldehydes is predicted to occur via cyclic transition states yielding syn-nitro alcohols as major products (Eq. 3.64).108... 

Method B In contrast, reprotonation of the tert-butyldimethylsilyl-protected nitronate anions gives awh-isomers selectively (41 9-19 1). 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

The addition of alkyl nitronate anions to imines in the presence of a Lewis acid proceeds in high yield with up to 10 1 diastereoselection favoring the anti isomer. This reaction is used for the stereoselective synthesis of 1,2-diamines (Eq. 4.121).167 Scandium triflate catalyzes the addition of 1-trimethylsilyl nitropropanoate to imines with a similar selectivity.35... 

Nitronate anions react with (jl-allyl)cobalt complexes prepared from acylation of 1,3-dienes by acetylcobalt tetracarbonyl to produce nitro enones (Eq. 5.50).74... 

Dimethyldioxirane oxidation of nitronates anions affords the corresponding carbonyl products. Highest yields are obtained when one equivalent of water is added before the oxidation (Eq. 6.9).17... 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

However, the character of the reaction of 3-nitro-substituted TV-oxide (169) with the C,C triple bond is changed 371. Apparently, the first step affords the normal cycloadduct A, which is successively rearranged into aziridine B. Elimination of the nitronate anion from the latter compound gives rise to ambident cations C and D, which, after quenching with methanol, form dihydrooxazines (170) or (171) depending on the nature of the substituent R. 

The chlorodifluoromethylated ketone 130 proved to be a valuable substrate for promoting SrnI subtitution reaction with sodium phenylthiolate and to generate a new a-(phenylthio)-a,a-difluoroacetophenone derivative 131 (Equation 57) <2001TL3459>. Upon treatment with nitronate anions under classical SrnI reaction conditions or MW irradiation, 6-chloromethyl-5-nitro-imidazo[2,l- ]thiazole 132 yielded 5-nitroimidazothiazoles bearing a trisubstituted ethylenic double bond at the 6-position (Equation 58) <2001SC1257>. 

Other anions such as nitronate anion,96 or the conjugate base of (3-ketoesters,97 give similar results. Usually, the 1,2-cw-C-glycosyl compound is formed under kinetic conditions. Thus, in the case of the reaction of the GlcNAc derivative 75 with the Wittig reagent Ph3P=CHCOOEt, the a-C-pyranosyl compound 77a is the major product under conditions of kinetic control. Under basic conditions, 77a is slowly epimerized into the more stable (3-C-pyranosyl derivative 77p (Scheme 25). 

Alkylation of nitronates is a complex chemical reaction. Due to the ambident character of the nitronate anion, nitronates can be alkylated either at the carbon or at the oxygen atoms. The mechanism of this reaction... 

Reactions of aliphatic nitro compounds with nucleophiles have been reviewed442-444. The oxidative reaction of nitronate anions, e.g. 410, with thiocyanate anions to yield thiocyanates 411 proceeds by a radical radical-anion chain mechanism SrnI (equation 133). Analogous replacements by azide, benzenesulphinate and 4-chlorobenzenethiolate have been reported445. 

The nitronate anion 414 derived from phenylnorbornene reacts with benzenesulphinate, thiocyanate, nitrite or 4-chlorobenzenethiolate anions in the presence of Fe(III) by the Siwl mechanism to give the norbornenes 415 (R = C SPh, SCN, O2N, or SC6H4CM, respectively). No cyclization occurred450. 

Time-resolved resonance Raman spectroscopy has been used to study the photorearrangement of o-nitrobenzyl esters in polar and protic solvents53 in acetonitrile, the only primary photoproduct is nitronic acid 68 with a lifetime of 80 microsecond, while in methanol the nitronic acid exists in equilibrium with the nitronate anion 69, giving a lifetime of 100 microseconds (equation 41). 

The conjugate 1,4-addition of nitronate anions and other nucleophiles to a-nitroalkenes constitutes an important method for the synthesis of polynitroaliphatic compounds. ° Nitroform (112) reacts with nitroethene (135) and 2-nitropropene to yield 1,1,1,3-tetranitropropane (136) and 1,1,1,3-tetranitrobutane respectively. A number of examples of additions of 1,1-dinitroethane, 1,1-dinitropropane and 1,1-dinitrobutane to nitroalkenes have been reported. Feuer and co-workers reported the synthesis of 1,3,3,6,6,8-hexanitrooctane (137) from the reaction of 1,1,4,4-tetranitrobutane (30) with nitroethene under basic conditions. 

Nielsen and Bedford synthesized gem-dinitroalkanes (147) from the Michael addition of organolithium reagents to a-nitroalkenes (146) followed by quenching of the resulting nitronate anion with tetranitromethane. The same reaction using alkoxides as bases provides P-alkoxy-gem-dinitroalkanes (148). ... 

Mannich bases derived from polynitroalkanes are usually unstable because of the facile reverse reaction leading to stabilized nitronate anions. The nitration of Mannich bases to nitramines enhances their stability by reducing the electron density on the amine nitrogen through delocalization with the nitro group. The nitration of Mannich bases has been exploited for the synthesis of numerous explosives, some containing both C-NO2 and N-NO2 functionality. Three such compounds, (163), (164) and (165), are illustrated below and others are discussed in Section 6.10. 

The use of polynitroaliphatic alcohols as sources of the corresponding nitronate anions is common in addition reactions. However, polynitroaliphatic alcohols are useful in their own right. The hydroxy functionalities of 2,2-dinitroethanol, 2,2-dinitro-l,3-propanediol and... 

Paquette and co-workers synthesized the 5,11-dinitro isomer of 1,3-bishomopentaprismane (95) by treating the dioxime (94) with a buffered solution of m-CPBA in refluxing acetonitrile. A significant amount of lactone by-product (96) is formed during this step and may account for the low isolated yield of (95). Oxidative nitration of (95) with sodium nitrite and potassium ferricyanide in alkaline solution yields a mixture of isomeric trinitro derivatives, (97) and (98), in addition to the expected 5,5,11,11-tetranitro derivative (99), albeit in low yield. Incomplete reactant to product conversion in this reaction may result from the low solubility of either (97) or (98) in the reaction medium, and hence, incomplete formation of the intermediate nitronate anions. 

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