Nitrones intermediates

R = H, Scheme 27). On the other hand, reaction of 255a with N-methylhydrox-ylamine hydrochloride produces a mixture of two regioisomers 257 and 258 (R = Me). When the E-l(10)-unsaturated 5-oxo-5,10-secosteroid 255b was treated with hydroxylamine hydrochloride (R = H) or AT-methylhydroxylamine hydrochloride (R = Me), isoxazolidine 259 was formed regio- and stereoselec-tively in high yield via intramolecular 1,3-dipolar cycloaddition of the nitrone intermediate 256 (R = H or Me). 

The 1,4-addition of RMgX or RLi to nitroalkenes produces nitronate intermediates, which are converted into nitroalkanes, nitrile oxides (oxime chlorides), or carboxylic acids, depending on the conditions of hydrolysis (Scheme 4.14).94... 

Oxidation of the retrain dm-oxazolo[3.2-/,) isoxazolc 119 followed by a spontaneous fragmentation of the transient A-oxide resulted in the nitrone intermediate 120. Acidic methanolysis of this latter liberated the /5-hydroxy ketone 121 (Equation 52) <1995JOC1720>. 

The reaction of compounds 465 with an excess of aryl isocyanate in acetonitrile at reflux leads to the formation of imidazooxadiazolones 466, via a Beckmann fragmentation that affords a presumed cyclic nitrone intermediate 187 (Equation 107) <1999SC3889>. 

An alternative procedure that generates stable, storable nitrone intermediates 175 from 170, mediated by dry m-CPBA as oxidating reagent, is shown in Scheme 77 ". Conversion of the nitrone 175 to the hydroxylamine by an exchange reaction with hydroxylamine hydrochloride was followed by EDC/HOAt-mediated cyclization to hydroxamic acid 174 (HOAt l-hydroxy-7-azabenzotriazole). 

Grigg and co-workers (310) recently examined the 1,3-APT reaction of various aldoximes (270) (R or R = H) with divinyl ketone (Scheme 1.56). While ketoximes 270 (R = R) form a mixture of adducts, 271 and 272 via nitrone 273, the aldoximes selectively afford 272 (as a mixture of endo and exo diastereoisomers). Under the thermal reaction conditions, the oxime starting materials can undergo ( /Z) isomerization, while the nitrone intermediate was expected to be unaffected and the isolated cycloadducts showed no interconversion via cycloreversion. Thus, the increasing selectivity for endo-212 [via ( )-273, R = H] over exo-212 [via (Z)-273, R = H] with the increasing size of the aldoxime substituent was attributed primarily to the inhibition of oxime isomerization by steric clash between R or R and the oxime OH. In contrast, Lewis acid catalysis, in particular by hafnium (iv) chloride, of the cycloaddition of various aldoximes with this dipolarophile gave exo-271 exclusively (216). 

The chemistry involves an unstable/explosive nitronate intermediate [17] bromonitromethane is a class I explosive. 

Unsaturated oximes can be cyclized simply by heating.24b It has been suggested that nitrone intermediates are involved in this process. Thus, oxime (53) on heating at 180 °C cyclized to a pyrrolizidine in 60% yield presumably tautomerization to nitrone (54) first occurred followed by [3 + 2] cycloaddition (Scheme 14). Likewise, quinolizidine (55) was obtained in 69% yield from the corresponding oxime. 

Sn-chelated glycine ester enolates have been proved efficient nucleophiles for highly stereoselective 1,4-additions toward nitroalkenes.37 In the presence of acyl halides the tin also acts as a reducing agent of the nitronate intermediates, giving direct access to nitriles in a one-pot protocol. 

When 3,4-disubstituted /3-lactam 457 was treated with methylhydroxylamine hydrochloride in the presence of sodium carbonate in methanol, a quantitative yield of an isomeric mixture of fused adduct 458 and bridged isoxazolidine 459 in a 15 1 ratio, respectively, was obtained (Equation 72) via a nitrone intermediate <1999TL5391>. 

Organomagnesium compounds add to polycyclic aromatic hydrocarbons under forcing conditions, bnt with electron-withdrawing substituents the addition occurs more easily. Alkyl Grignard reagents add 1,4 and/or 1,6 to nitroaromatics, and the nitronate intermediate may be converted to a number of useful products (equation 45). Aryl Grignards yield hydroxylamines (by means of a 1,2 process), which can be reduced to diarylamines. ... 

Trialkylboron hydrides react with conjugated nitroalkenes to yield nitronate intermediates via a 1,4-addition of the hydride. The corresponding nitroalkanes are easily obtained by using silica gel to proto-nate the nitronate salt. These reactions presumably occur through a common intermediate (36), which is then hydrolyzed to the nitroalkane or reduced by a borane complex to yield hydroxylamine, after hydrolysis. 

Pandey and coworkers have studied the DCN-sensitized oxidation of N-hydroxyamines without prior removal of dissolved oxygen, to nitrone intermediates. Trapping the nitrones by dimethylfumarate (282) gave the corresponding cycloadducts in good yields (Scheme 66) [317]. 

Aromatic nitro-compounds can be made to condense with silyl-enol-ethers using tris(dimethylamino) sulfur (trimethylsilyl)difluoride (TASF) a non-aromatic nitronate intermediate is aromatised by reaction with bromine, without isolation, to provide a 2-(orf/to-nitroaryl)-ketone and thence an indole after nitro group reduction. ... 

By examining Scheme 1 it is possible to verify the key role of the base as catalyst for the overall process and to justify the lack of stereoselectivity which, in general, has been observed in nitroaldol additions. In fact, the reversibility of the nitroaldol process, as well as the difficulty of a stereoselective protonation of the stereogenic center of the nitronate intermediates, leads to a mixture of diastereomeric 2-nitro alcohols. 

Treatment of synlanti mixtures of aldoximes (69) with allylboronates generates N-(homoallyl)hydrox-ylamines (70) in good yield (Scheme 6). - The anti oxime reacts faster than the syn isomer. N-(Ho-moallyl)hydroxylamines (70) have been converted to homoallylamines (71) (with iron(II) dihydrolipoate) and have been treated with aldehydes to generate highly functionalized nitrone intermediates (72) for use in 1,3-dipolar addition reactions. 

In contrast to the complete regioselectivity observed in the 1,3-dipolar cycloaddition of nitronate 16b and methyl crotonate 42 or methyl cinnamate 44 shown in Scheme 9.14, the [3 -t 2] cycloaddition of yS-nitrostyrene (15a) and nitronate intermediate 16a was not completely regioselective. Regio-isomers 46 and 47 were formed in 83 % yield, as mixtures of diastereomers, in a 7 3 ratio after the high pressure-promoted domino cycloaddition of enol ether 14 with 2 equiv. fi-nitrostyrene (15a) (15 kbar, RT, 18 h, Scheme 9.15). The formation of regio-isomer 46 as major product was rather unexpected, since comparable 1,3-dipolar cycloadditions of nitrones and nitroalkenes [25] showed the opposite regio-isomer to be formed predominantly. This nitroso acetal (46) was converted to )S-lactam (48) via a base-catalyzed rearrangement (Scheme 9.16). This conversion appeared applicable to different hi- and tricyclic nitroso acetals and led to the formation of a novel class of bi- and tricyclic yS-lactams [26]. 

The reaction of a trinitromethyl halide with diazomethane gives a nitrone intermediate, which can be trapped by a suitable olefin.124-127... 

Cycloaddition reactions as an approach to nitrogen- and oxygen-containing heterocycles have dominated the literature this year and are the topic of the remainder of this section. The intramolecular cycloaddition of aryl oxaziridines to give fused isoxazolidines (71) proceeds in good yield, presumably via a nitrone intermediate. On the other hand the oxime (72) undergoes an intramolecular cycloaddition to give the isoxazolidine (73) and can either be... 

Nitrone intermediates have been used in syntheses of hadacidin (13) (189), alanosine (18) (190), -hydroxyornithine (73) and N -hyd-... 

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