Trimethylaluminum-assisted alkynylation of nitrones

Reaction of nitrones with terminal alkynes occurs in the presence of 1 equiv of trimethylaluminum and leads to the corresponding propargylic hydroxylamines in yields ranging from 49 to 90%.     

Dialkylzinc-assisted alkynylation of nitrones

[reaction: see text]. Reaction of nitrones with terminal alkynes takes place readily in the presence of a substoichiometric amount of diethylzinc in toluene, affording N-propargyl-hydroxylamines in excellent yields and purity.     

Diastereoselective intermolecular radical addition to nitrones

The intermolecular radical addition to chiral nitrones 2, 4, 5, and 16 was studied. The isopropyl radical addition to Oppolzer's camphorsultam derivative 2 of glyoxylic nitrone proceeded with excellent diastereoselectivity to give the desired isopropylated product 3a accompanied by the diisopropylated product 3b. A high degree of stereocontrol in the reaction of cyclic nitrone 4 was achieved. The ethyl radical addition to nitrone 4 with triethylborane afforded the desired ethylated product 9a accompanied by the diethylated product 10a and the ethylated nitrone 11a. To evaluate the utility of cyclic nitrone 4, several alkyl radicals were employed in the addition reaction, which afforded the alkylated products 9b-d with excellent diastereoselectivities. In the presence of Mg(ClO(4))(2), the ethyl radical addition to BIGN 16 afforded selectively syn isomers. In contrast, the alkyl radical addition to 16 took place even in the absence of Lewis acid to give anti isomers.     

A general synthesis of N-vinyl nitrones

A general synthesis of a new type of heterodiene, the N-vinyl nitrone, is described. The synthetic sequence begins with the conjugate addition of benzeneselenol to nitroalkenes (in turn derived from Henry reaction of an aldehyde and a nitroalkane) to provide 2-selenenylnitroalkenes. These selenonitroalkanes are reduced to the corresponding hydroxylamines which are combined with aldehydes to form nitrones. The phenylselenenyl-containing nitrones are then oxidized to selenoxides which undergo syn-selenoxide elimination to provide N-vinyl nitrones. Three X-ray crystal structures of substituted N-vinyl nitrones were obtained. In addition, the first [4+2] cycloaddition of an N-vinyl nitrone is reported.     

Synthesis of N-alkyl-N-hydroxyamphetamines and related nitrones

The action ofm-chloroperbenzoic acid on various amphetamines and on dibenzylamine is shown to yield N-hydroxy derivatives and related nitrones.     

Formation and cycloaddition reactions of ferrocenyl nitrones

Ferrocenyl nitrones derived from aldehydes or oximes react with electron deficient alkenes to give ferrocenylisoxazolidines. 5‐Methoxycarbonylisoxazolidines are further transformed to ferrocenyl‐pyrrolidinones by reductive cleavage. The regio‐ and stereoselectivity of the reactions are discussed.     

The cycloaddition of nitrones with homochiral cyclopropanes

The cycloaddition of nitrones and enantiomerically pure cyclopropane-1,1-dicarboxylates is examined. Transfer of optical activity to the adduct is dictated by thermal reaction conditions and nature of cyclopropane substitution. Optically active 2-substituted cyclopropane-1,1-dicarboxylates are shown to racemize under typical reaction conditions, providing evidence for a zwitterionic ring-opened intermediate.     

Diastereoselective addition of alkynylalanes to carbohydrate-derived nitrones

Propargylic N-hydroxypyrrolidines were prepared by diastereoselective addition of pre-formed alkynylalanes to various highly functionalized carbohydrate-derived endocyclic nitrones. Excellent diastereoisomeric excesses were obtained using dimethyl-2-phenylethynylalane. Addition of other alkynylalane derivatives to such type of nitrones is also reported.     

Reactions of nitrones with di- and tetrahydropyrans

N-(Benzylidene)- and N-(2-phenylamino-2-oxoethylidene)aniline N-oxides add stereospecifically to the double bond in 4-methylene- and 4-acryloylamino-4-methyltetrahydropyrans to give substituted isoxazolidines. The use of 4-methyl-5-arylamino- and 4-arylaminomethyl-5,6-dihydro-2H-pyrans for the synthesis of novel N-oxides has given tricyclic adducts resulting from intramolecular cyclization of the required compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1113–1116, August, 1990.     

Asymmetric Kinugasa reaction involving six-membered cyclic nitrones

Kinugasa reactions between terminal acetylenes and six-membered ring nitrones when one or both components are chiral, proceed in a low to moderate yield and with a high diastereoselectivity affording mostly one, dominant β-lactam product. The first step of the reaction is controlled by the configuration of the nitrone, whereas the protonation of the C-7 center of the carbacepham skeleton in the second step depends on: a) the configuration of the bridgehead carbon atom formed in the first step, b) epimerization process in the presence of a base, and c) on the configuration of the stereogenic center in the acetylenic partner. In the case of the nitrone derived from dihydroisoquinoline, the reaction proceeds in a more complex way affording not only β-lactams, but also products derived from the alternative regio-1,3-cycloaddition, or nucleophilic addition of the acetylene to the double bond of the nitrone.     

Dipolar 1,3-cycloaddition reaction of conjugated nitrones

Conclusions Some new isoxazolidines were synthesized by the 1,3-dipolar cycloaddition reactions of conjugated nitrones (–CH=CH–CH=N0) with activated dipolarophiles.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 908–910, April, 1974.     

Enantioselective addition of nitrones to activated cyclopropanes

In this paper, we demonstrate the first examples of chiral Lewis acid catalysis in the formation of tetrahydro-1,2-oxazines with very high enantioselectivity starting with diactivated cyclopropanes and nitrones (>90% yields and ee). Reactions with racemic substituted cyclopropanes provide approximately 1:1 diastereomeric tetrahydro-1,2-oxazine products with high enantioselectivity. Mechanistic information for the formation of the tetrahydro-1,2-oxazines is also detailed.     

Solvent-free synthesis of nitrones in a ball-mill

Various C-aryl and C-alkyl-nitrones were synthesized within 0.5–2 h via condensation of an equimolar amount of aldehydes and N-substituted-hydroxylamines under solvent-free conditions in a ball-mill apparatus. Reactions can be performed without the need of excluding air and moisture and yields the expected products with no need for further purification. The study has been complemented by Differential Scanning Calorimetry (DSC) and solid-state ¹³C MAS nuclear magnetic resonance experiments. We have also studied the temperature profile during the reaction. A comparative study with the corresponding solvent-free microwave activated reaction showed the superiority of the ball-milling method; 31 examples are described, including the synthesis of the anti-aging agent C-phenyl-N-tert-butyl nitrone (PBN) and one of its analogues C-2-pyridyl-N-tert-butylnitrone (2-PyBN).     

Synthesis of O-glycosylα-aryl nitrones

<正>α-Aryl nitrone are one of the most useful kinds of nitrones and have been extensively explored in recent years.However,the sugar moieties have not been introduced into these molecules before.We presented here an efficient synthesis ofα-aryl nitrone Oglycosides via condensation of N-substituted hydroxylamine and aryl aldehydes glycosides in benzene.     

Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrones.

Efficient routes to the synthesis of norbornadiene-tethered nitrones have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in moderate to good yields for a variety of substrates and were found to be highly regio- and stereoselective, giving single regio- and stereoisomers in most cases.     

Improved dimethylzinc-promoted vinylation of nitrones with vinylboronic esters

Vinylboronic esters derived from 4,4,6-trimethyl-[1,3,2]dioxaborinane react with nitrones in the presence of dimethylzinc; nucleophilic addition of the vinyl group onto nitrones produces N-allylic hydroxylamines in fair yields. The sequence is compatible with various functional groups on the vinylic moiety. The mechanism and kinetic aspects are discussed on the basis of DFT calculations.