Nitrones from nitro-ketones

In spite of the obvious simplicity, this approach has not been examined in practice until recent years. In the very recent past, French researchers demonstrated that this approach can be used for the synthesis of five-membered nitronates 5c,d starting at least from nitro ketones (17a) containing the PhS substituent at C-2. These ketones have been generated from the corresponding 3-nitroenones (Scheme 3.20) (69). 

Severin and coworkers advantageously used dimethyl sulfate for the preparation of O-methyl nitronates from a representative series of conjugated vinyl ketones containing the nitro group in the allylic position (14) (Scheme 3.6, Eq. 3). 

As reported in Figure 2.5, nitroolefins (26), easily obtained by nitroaldol condensation between 5-nitro ketones (24) and aldehydes (25), are converted directly into the spiroketals (29) by reduction with sodium boronhydride in methanol. The one-pot reduction-spiroketalization of nitroalkenes (26) probably proceeds via the nitronate (27) that by acidification is converted into carbonyl derivatives, which spontaneously cyclize to emiketals (28). Removal of the tetrahydropyranyl group, by heating the acidic mixture during the workup, affords, in a one-pot reaction from (26), the desired spiroketals in 64-66% overall yields. The spiroketalization of (26)-(29b) proceeds in high ( )-diastereoselectivity. 

The a-hydrogens of nitroalkanes are appreciably acidic due to resonance stabilization of the anion [CH3NO2, 10.2 CH3CH2NO2, 8.5]. The anions derived from nitroalkanes give typical nucleophilic addition reactions with aldehydes (the Henry-Nef tandem reaction). Note that the nitro group can be changed directly to a carbonyl group via the Nef reaction (acidic conditions). Under basic conditions, salts of secondary nitro compounds are converted into ketones by the pyridine-HMPA complex of molybdenum (VI) peroxide. Nitronates from primary nitro compounds yield carboxylic acids since the initially formed aldehyde is rapidly oxidized under the reaction conditions. 

The photoreactions (X >435 nm in dichloromethane) of tetranitromethane (261) with styrenes (260) to yield nitro-trinitromethyl adducts (269), diastereo-meric oxazolidines (270), nitro ketones (271) and nitronic esters (272) may be rationalised in terms of the interlinked pathways in Scheme 3. SET yields nitrogen dioxide (262), the styrene radical cation (263) and the trinitromethanide ion (264). Addition of nitrogen dioxide (262) to the styrene (260) initiates a radical chain process. Benzylic radical (266) is oxidised by tetranitromethane (261) to the benzylic cation (265). Nitro-trinitromethyl adducts (269) result from coupling of the cation (265) with the anion (264). A competing pathway involves reaction of radical cation (263) with anion (264). C clisation of the resulting radical (268) yields the aminoxyl (267), from which loss of nitrogen dioxide yields the nitronic ester (272), whereas coupling of (267) with the radical (266) forms oxazolidine diastereomers (270). The nitroketones (271) may arise, at least in part, from secondary photolysis of the oxazolidines (270). ... 

The preparation of nitrones from aliphatic nitro ketones can also be carried out under transfer hydrogenation conditions with ammonium formate and Pd/C in 48-78% yields. ... 

Nef reaction.4 Nitro compounds, primary or secondary, are converted to tri-alkylsilyl nitronates in greater than 90% yield by reaction with a trialkylsilyl chloride and DBU in CH2C12. The silyl nitronates derived from secondary nitro compounds are oxidized by C1QH4C03H at 25° to ketones in high yield. This sequence is not useful for conversion of primary nitro compounds to aldehydes. 

Photolysis of nitro-steroids 225 yields the aci-nitronate at 254 nm131. This in turn gives various products, among them are ketone 226 and hydroxamic acid 227 (equation 105) which could be formed from the intermediate anions of the Af-hydroxyoxaziridines, with a possible participation of gem-hydroxynitroso transient (or its anion see Scheme 10). For comparison, IV-butyl spiro-oxaziridine 228 in ethanol is photolysed at 254 nm (equation 106) to give 7V-butyl lactam 229 (50%) and the ketone 230 (25%). The former process is a well-known photoprocess of oxaziridine131. 

Nickel, dichloro [ethylenebis(dimethyl-phosphine)], 58, 133 Nickel, dichloro[ethj lenebis(diphenyl-phosphine)], 58,133 [Ni (-)-diop Cl2 ], (-)-diop=2,3-0-iso-propylidene-2,3-dihydroxy-l,4-bis(di-phenylphosphino)butane, 58, 133 Nickel, dichloro [ trimethylenebis(diphenyl-phosphine)], 58,133 NITRILES, alkylation of, 55, 91 NITRILES FROM KETONES, 58, 101 NITRILES, a vinyl, 55, 99, 101 p-Nitrobenzenesulfonyl cyanide, 57, 89 p-Nitrobenzyl alcohol, 57, 72 p-NITROBENZYL FLUORIDE, 57, 72 Nitro compounds, 56, 36 Nitronates, 56, 36... 

Removal of a proton from an aliphatic nitro compound gives a carbanion (R2C —NO2) that can be alkylated at oxygen or carbon. 0-Alkylation gives nitronic esters, which are generally unstable to heat but break down to give an oxime and an aldehyde or ketone. 

Because the nitrogen in nitro compounds is at the highest oxidation state, nitro compounds can be oxidized only in the carbon chain to which the nitro group is attached. The oxidation of primary and secondary nitro compounds in the form of their nitronic acids in alkaline medium by potassium permanganate represents a variation of the Nef reaction and gives the same products aldehydes from primary nitro compounds and ketones from secondary nitro compounds (equation 484) [867],... 

The reaction of nitromethane with an acceptor such as methyl vinyl ketone can proceed in water without the assistance of a base (see Scheme 10.8 in Sect. 10.2.2) [69]. The rate constant is low at ambient pressure, but is considerably increased with the aid of pressure [36]. The slight acidity of the nitro compound makes the nitronate a suitable base. However, the formation of the enolate requires assistance. In view of the very negative value of the volume of activation (—35.5 cm mol ) it is suggested that an electrostatic volume term must be taken into account together with a volume contribution arising from the specific interaction of water with the activated complex. 

The Nef reaction1 2 is the conversion of nitroalkanes to ketones and aldehydes through treatment with base followed by acid.3 4,5,6 For example, deprotonation of 1-nitrobutane (1) with aqueous NaOH followed by addition of excess aqueous sulfuric acid afforded butyraldehyde (2) in 85% yield (isolated as the oxime derivative).7 These reactions proceed via intermediate nitronate anions, which are subsequently hydrolyzed to afford the carbonyl products. The overall transformation leads to formal polarity reversal of the carbon bearing the nitro group from a nucleophilic species to an electrophilic carbonyl carbon. Although the classical conditions for this process are quite harsh, a number of alternative procedures that employ mild reaction conditions have been developed. 

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