Ketones from nitronic acids

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],... 

Chiral cyclic nitrones (185) were synthesized in the reaction of isonitroso-derivatives of Meldmm s acid (183) with ketones in boiling toluene (338—344). The reaction is likely to proceed, as in the case of the cycloaddition of a-nitrosostyrenes, by [3 + 2] cycloaddition of ketones to nitrosoketone (184), resulting from thermolysis of (183) (Scheme 2.65) (345). 

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. 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

Elimination of sulfinic acid from ketosulfones was also a key step in an expedient synthesis of a,0-unsaturated ketones via the Michael adducts of sulfonyl carbanions to nitroalkenes. Conversion of the resulting nitronates into ketones was most conveniently realized by ozonolysis. DBU-promoted elimination of sulfinic add completed the process. Overall yields range from 71 to 88% for the examples reported [425]. 

Cyclic nitrones, which are commonly formed by cycloaddition of ketones to nitrosoketene, can also be obtained by pyrolysis of 5-isonitroso-2,2-dimethyl-l,3-dioxane-4,6-dione (73) (isonitroso Mcldrum s acid) in the presence of various ketones. Two possible reaction pathways (Scheme 8) have been proposed previously to account for formation of cyclic nitrones from (73), but the proposed nitrosoketene intermediate could not be observed. Spectroscopic evidence for generation of the nitrosoketene in the gas phase at > 80 °C has now been found and ab initio calculations in support of the vibrational frequencies observed have been reported.35... 

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. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

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 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. 

Aminoalkylquinoxalines (17) have been derived from a-amino acids (10) as shown in Scheme 2, the amino group is protected by formation of a phthalimide derivative (11). The intermediate chloromethyl ketone (12) is converted via a pyridinium salt (13) to a nitrone (14) which on hydrolysis yields the a-dicarbonyl compound (15) required for diamine condensation. Finally the phthalimide residue is removed from the condensation product (16) by hydrazine treatment. ... 

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. 

Thermolysis of the hydroxyimino derivative 40 of Meldrum s acid generates nitrosoketene 41, which adds to ketones to give cyclic nitrones, e.g. 42 from cyclohexanone (94CC281). Methyl (Z)-3-dimethylamlno-2-i3ocyanoacrylate reacts with acyl chlorides to give 2-acyl-4-(dimethyl-aminomethylene)oxazolin-5-ones 43 (93JHC575). 

Functionalization Reactions of Silyl Nitronates. Silyl nitronates can be used for a number of transformations in which the carbon skeleton is not changed. Thus they are intermediates en route from nitroalkanes to ketones (the transform of the Nef reaction). Peroxy acid treatment converts silyl nitronates, which would not survive the classical conditions of the Nef reaction, to ketones (eq 8). Aldehydes can be obtained analogously, using stannyl nitronates. ... 

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