Diketone nitroalkane

Trialkylisoxazoles have been prepared by the condensation of primary nitroalkanes under the influence of basic reagents (40JA2604). They can also be obtained from the reaction of a 1,3-diketone RCOCHRCOR with hydroxylamine hydrochloride <62HC(17)l, p. 54). 

The photochemical cyclisation of p.y-unsaturated ketoximes to 2-isoxazolines, e.g., 16—>17, has been reported <95RTC514>. 2-Isoxazolines are obtained from alkenes and primary nitroalkanes in the presence of ammonium cerium nitrate and formic acid <95MI399>. Treatment of certain 1,3-diketones with a nitrating mixture generates acyl nitrile oxides, which can be trapped in situ as dipolar cycloadducts (see Scheme 3) <96SC3401>. 

Both overt carbanions and organometallic compounds, such as Grignard reagents, are powerful nucleophiles as we have seen in their addition reactions with C=0 (p. 221 et seq.) they tend therefore to promote an SN2 pathway in their displacement reactions. Particularly useful carbanions, in preparative terms, are those derived from CH2(C02Et)2, (3-ketoesters, l,3-( 3-)diketones, e.g. (55), a-cyanoesters, nitroalkanes, etc.—the so-called reactive methylenes ... 

Conjugate addition of nitroalkanes to ailyl Baylis-Hillman acetates in the presence of NaOH (0.6 N) in THF gives 2-alkylidene-4-nitro ketones with high stereoselectivity these are converted via the Nef reaction into the corresponding 1,4-diketones (Eq. 4.119).164... 

The Nef reaction can also be carried out with reducing agents. Aqueous titanium chloride reduces nitro compounds to imines, which are readily hydrolyzed to carbonyl compounds (Eq. 6.17).28 The Michael addition of nitroalkanes to enones followed by reaction with TiCl3 provides an excellent route to 1,4-diketones and hence to cyclopentenones. For example, cw-jasmone is readily obtained,28 as shown in Eq. 6.18. 

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. 

Conjugate addition of RN02 to enones. Primary nitroalkanes and a, (3-enones when activated by alumina form conjugate addition products that are oxidized in situ by alkaline hydrogen peroxide to 1,4-diketones. A similar reaction of nitromethane with a vinyl ketone provides 1,4,7-triketones. 

Phenylation, of 3-diketones with diphenyliodonium chloride, 51, 131 of ketoesters with diphenyliodonium chloride, 51, 131 of nitroalkanes with diphenyliodonium chloride, 51, 132 PHENYLATION WITH DIPHENYL-... 

Electrophilic nitrations of aliphatic nitriles, carboxylic acids,carboxylic esters, ° and /3-diketones have been reported. The nitration of 2-alkyl-substituted indane-l,3-diones with nitric acid, followed by alkaline hydrolysis, is a standard laboratory route to primary nitroalkanes. ... 

Nitroalkanes (Tables 12 and 13) These are possibly among the most useful substrates for reaction with the superoxide/dioxygen reagent, and the loss of nitrite, according to Scheme 21, has been confirmed. Secondary nitroalkanes are efficiently converted into ketones (Table 12), and the reaction may prove to be of especial value for the preparation of 1,4-diketones. 

The /V-(2,6-dimethy 1-4-oxopyridin-1 -yl)pyridinium salts (15)24 have proved to be versatile intermediates for the regiospecific synthesis of 4-substituted pyridines (17) via attack by the appropriate carbon nucleophiles, e.g. ionized ketones,90 nitroalkanes,91 esters and nitriles,92 and a-diketones, a-keto esters, a-diesters, disulfones etc. (Scheme 10).93 Aromatization of the intermediate 1,4-dihydro adduct (16) was generally achieved under free radical conditions. 

The synthetic methods which are illustrated in this section are (a) the formation of symmetrical 1,4-diketones from 1,3- (or / -)keto esters (Expt 5.104), and (b) a Michael addition reaction involving nitroalkanes and a, /f-unsaturated ketones (Expt 5.105). The synthesis of symmetrical 1,4-diketones from the sodio derivatives of /f-keto esters, or their mono-alkyl derivatives, by treatment with iodine [Method (a)], may be formulated in the following general manner. 

Nef transformation,3 A versatile route to 1,4-diketones involves Michael addition of a nitroalkane to an a,/J-enone, which can be effected in 80% yield when catalyzed by fluoride ion (9, 446-447). The resulting y-nitro ketone is oxidized efficiently by a stoichiometric amount of KMn04 impregnated on silica gel to a 1,4-... 

The synergy between nitroalkanes and aqneons medium has been the key idea for the one-pot synthesis of 8-nitroalkanols (38) as shown in Figure 2.8, hydroxytetrahy-drofurans (lactols) (39), 1,4-diketones (40), and 1,4-diols (41). 

Ballini, R., Barboni, L., and Giarlo, G. 2003a. Nitroalkanes in aqueous medium as an efficient and eco-friendly source for the one-pot synthesis of 1,4-diketones, 1,4-diols, 5-nitroaIkanols, and hydroxytetrahydrofurans. Journal of Organic Chemistry, 68(23) 9173-6. 

The resulting derivatives were applied with success in the standard asymmetric allylic alkylation (up to 97 % ee) [134, 136] or in transformations involving either specific allylic substrates (2-cycloalkenyl derivatives, up to >99% ee) [135, 137], unsymmetrical substrates (monosubstituted allyl acetate, up to 83% ee) [140], or especial nucleophiles (nitroalkanes [141], iminoesters [138 a], or diketones [139, 140, 142]). Such ligands were also effective in the formation of quaternary chiral carbon through allylic substitution (eq. (6)) [138, 143], deracemiza-tion of vinyl epoxides (up to 99% ee) [144], or alkylation of ketone enolates [138 b], and deracemization of allylic derivatives [145]. 

The electrophilic PhCOCH2 radical generated by photolysis of PhCOCH2HgCl in DMSO adds readily to enamine 10b to form the substituted enamine 18, which upon hydrolysis gives the 1,4-diketone 19 in 60% overall yield. In this free radical chain reaction (Scheme 2), the electron transfer from the easily oxidizable adduct radical 17 to PhCOCH2HgCl is facilitated by the fact that the irreversible half-wave reduction potentials of alkylmercury halides are typically more positive than — 0.6 Silyl derivative 20 of an reacts with morpholine enamine 2 in the presence of 2.5 equivalents of manganese(III) 2-pyridinecarboxylate [Mn(pic)3] to give... 

A synthesis ofstrigol using nitroalkanes Synthesis of mono-protected diketones Catalytic Methods The Stetter Reaction... 

Michael additions go particularly well with nitroalkanes with catalytic base because the first formed enolate is more basic than the nitroalkane. Diketones, e.g. 159, keto-aldehydes and keto-acids can all be made by this route and the two steps can be combined in one using alumina to catalyse the Michael addition (158 is not isolated) and an oxidative work-up to release the ketone.34... 

Manganese(III) can oxidize carbonyl compounds and nitroalkanes to carboxy-methyl and nitromethyl radicals [186]. With Mn(III) as mediator, a tandem reaction consisting of an intermolecular radical addition followed by an intramolecular electrophilic aromatic substitution can be accomplished [186, 187). Further Mn(III)-mediated anodic additions of 1,3-dicarbonyl and l-keto-3-nitroalkyl compounds to alkenes and alkynes are reported in [110, 111, 188). Sorbic acid precursors have been obtained in larger scale and high current efficiency by a Mn(III)-mediated oxidation of acetic acid acetic anhydride in the presence of butadiene [189]. Also the nitromethylation of benzene can be performed in 78% yield with Mn(III) as electrocatalyst [190]. A N03 radical, generated by oxidation of a nitrate anion, can induce the 1,4-addition of aldehydes to activated olefins. NOj abstracts a hydrogen from the aldehyde to form an acyl radical, which undergoes addition to the olefin to afford a 1,4-diketone in 34-58% yield [191]. 

Isomerization of epoxides. a, -Epoxy ketones and /S.y-epoxy nitroalkanes" undergo ring opening to give a-diketones and y-hydroxy nitroalkenes, respectively. 

Ketones from nitroalkenes. NaH2P02 is a good hydrogen donor in the pres- nce of a catalyst. Its combination with Raney nickel to convert nitroalkenes to ketones has been put to use in the general synthesis of 1,3-, 1,4-, and 1,5-diketones rom functionalized nitroalkanes. 

This reaction has general application in the synthesis of aldehydes and ketones, especially for 1,4-diketones and dihydrofurans. The 1,4-diketones can be prepared by the combination of a Michael reaction between a nitroalkane and an O, y0-unsaturated ketone followed by a Nef reaction, whereas dihydrofurans can be synthesized by the Nef reaction followed by cyclohydration. 

Bauchat et al have carried out reactions of MBH acetates with carbanions generated from a 1,3-diketone, methyl cyanoacetate or nitroalkane by treatment with potassium carbonate or potassium fluoride on alumina to provide trisubstituted olefins 182 and 183 with ( )-selectivity. These products were subsequently transformed into useful y-lactones 184 and 8-lactones 185, respectively (Scheme 3.73). 

Amri and co-workershave successfully transformed the acetates of the MBH adducts obtained from various activated alkenes into p-nitro-alkene derivatives via treatment with nitroalkanes. The resulting nitroalkane derivatives 234 and 235 were further transformed into the corresponding 1,4-diketones 236 and keto alkene derivatives 237 via a Nef reaction (Scheme 3.92). 

Soft carbon nucleophiles, such as activated methylene or methyne compounds 11, react with butadiene to give a mixture of the mono- (12) and di-(2,7-octadienyl) adducts (13) in the case of = H (activated methylenes), and to give the monoadduct 12 in the case of activated methynes, as expected (Scheme 3). The addition reactions with various carbon nucleophiles, such as j8-keto esters, /S-diketones, malonate and malononitrile, a-formyl ketones and esters, a-cyano ketones and esters, cyanoacetoacetamide, phenyl-sulfonyl acetate,nitroalkanes, and an enamine, are summarized in Table 1. PdCl2(PPh3)2-NaOPh is often used as a catalyst for the dimerization reaction. Complexes... 

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