Nitronic Esters Research Articles

Interrupted Nef Reaction of Cyclic Nitronates: Diastereoselective Access to Densely Substituted α-Chloronitroso Compounds.

The reaction of cyclic nitronic esters (isoxazoline- and 5,6-dihydro-4H-1,2-oxazine-N-oxides) with hydrochloric acid affords geminal chloronitroso compounds bearing a distant hydroxyl group. The reaction is usually diastereoselective, and in some cases stereodivergent formation of isomers at different temperatures is observed. The discovered process represents the first example of an interrupted Nef reaction of nitronic esters. DFT calculations support the initial formation of N,N-bis(oxy)iminium cations (key intermediates in the Nef reaction), which are intercepted by the chloride anion followed by ring opening. The synthetic utility of the resulting functionalized chloronitroso compounds in the Diels-Alder reaction with cyclopentadiene was demonstrated.

A molecular electron density theory study of the [3 + 2] cycloaddition reaction of nitronic ester with methyl acrylate

A molecular electron density theory study of the [3 + 2] cycloaddition reaction of nitronic ester with methyl acrylate

Understanding the Molecular Mechanism of the Rearrangement of Internal Nitronic Ester into Nitronorbornene in Light of the MEDT Study.

The characterization of the structure of nitronic esters and their rearrangement into nitronorbornene reactions has been analyzed within the Molecular Electron Density Theory (MEDT) using Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d) computational level. Quantum-chemical calculations indicate that this rearrangement takes place according to a one-step mechanism. The sequential bonding changes received from the Bonding Evolution Theory (BET) analysis of the rearrangement of internal nitronic ester to nitronorbornene allowed us to distinguish seven different phases. This fact clearly contradicts the formerly-proposed concerted pericyclic mechanism.

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

The tin(IV)-catalyzed reaction of β-nitrostyrene with (E)-3-methyl-1,3-pentadiene in toluene afforded two major nitronic ester cycloadducts in 27% and 29% yield that arise from the reaction at the less substituted diene double bond. Also present were four cycloadducts from the reaction at the higher substituted diene double bond, two of which were the formal cycloadducts of (Z)-3-methyl-1,3-pentadiene. A Friedel–Crafts alkylation product from the reaction of the diene, β-nitrostyrene, and toluene was also obtained in 10% yield. The tin(IV)-catalyzed reaction of β-nitrostyrene with (Z)-3-methyl-1,3-pentadiene in dichloromethane afforded four nitronic ester cycloadducts all derived from the reaction at the higher substituted double bond. One cycloadduct was isolated in 45% yield and two others are formal adducts of the E-isomer of the diene. The product formation in these reactions is consistent with a stepwise mechanism involving a zwitterionic intermediate. The initially isolated nitronic ester cycloadducts underwent tin(IV)-catalyzed interconversion, presumably via zwitterion intermediates. Cycloadducts derived from the reaction at the less substituted double bond of (E)-3-methyl-1,3-pentadiene underwent a [3,3]-sigmatropic rearrangement on heating to afford 4-nitrocyclohexenes. Cycloadducts derived from the reaction at the higher substituted diene double bond of either diene failed to undergo a thermal rearrangement. Rates and success of the rearrangement are consistent with a concerted mechanism possessing a dipolar transition state. An initial assessment of substituent effects on the rearrangement process is presented.

ChemInform Abstract: Unexpected Transformations: From 5-Glyco-4-nitrocyclohexenes to Bicyclic[3.3.1]oximes Through Isoxazoline N-Oxides.

Abstract Treatment of 5-glyco-4-nitrocyclohexenes with excess or equimolar sodium methoxide gave deacetylated sodium nitronates which, on reaction with Ac 2 O/py, led to chiral isoxazoline N -oxides (cyclic nitronic esters). Depending on the configuration of their respective sugar side-chains, base-catalyzed deacetylation of these nitronate esters yielded either a bicyclic [3.3.1] oxime or a deacetylated isoxazoline N -oxide.

Formation and sigmatropic rearrangement of PhCOC(NO 2) [dbnd]CH 2 cycloadducts of 1,3-cyclohexadiene: a theoretical study

Competing cycloaddition pathways for the reaction of 2-nitro-1-phenyl-2-propen-1-one with 1,3-cyclohexadiene were investigated employing computational methods. A bifurcating pathway was found for formation of nitroketone 3 and nitronic ester 5. A second bifurcating pathway was found for the formation of nitroketone 4 and enol ether 6. Sigmatropic rearrangements of two cycloadducts, nitronic ester 5 and enol ether 6, were also studied computationally. The reaction pathways were mapped using the B3-LYP/6-311G(d) method and relative energies for species 3– 6 were calculated at the same level. Solution-phase corrections were performed by the PCM method. The calculations for both bifurcating cycloaddition pathways indicate kinetic control with similar rate-determining activation energies. The nitroketone 3 is more stable than nitronic ester 5 by 5.3 kcal/mol and nitroketone 4 is more stable than enol ether 6 by 3.9 kcal/mol, consistent with the observed direction of sigmatropic rearrangement.

Polynitromethanes - Unique Reagents in the Synthesis of Nitro-Substituted Heterocycles

The aim of this account is to present the latest findings from studies of the reactions of polynitromethanes with unsaturated compounds and oxiranes, and to review how these processes have been used in the synthesis of highly functionalized nitro compounds and nitrogen- and oxygen-containing heterocycles. In addition, literature on unstable acyclic nitronic esters, key intermediates in the tandem, multicomponent heterocyclization reactions of strained olefins, electrophilic alkenes, acetylenes, and oxiranes, is analyzed.

Formation and [3,3]-sigmatropic rearrangement of O-allyl nitronic esters: a new route to γ,δ-unsaturated nitro compounds

O-Allyl nitronic esters that are obtained from tin(IV) catalyzed Diels-Alder reactions undergo thermal rearrangement to gamma,delta-unsaturated nitro compounds.

Acyclic nitronic esters: Generation and utilization in the synthesis of N-and O-heterocycles

The literature concerning the chemistry of acyclic nitronic esters is surveyed and analyzed with special reference to tandem heterocyclization of unsaturated compounds with acyclic nitronic esters as 1,3-dipoles.

Study of the reaction of trinitromethane with oxiranes

83 The reaction of olefins with polynitromethanes is a known method for the preparation of 3,3-dinitroisoxazolidines [1, 2]. Previously, we studied reactions of tetranitromethane and halotrinitromethanes with unsaturated compounds containing small rings [3–8]. It was shown that the reactions of polynitromethanes with strained alkenes and acetylenes give a range of Nand O-containing heterocycles (dinitroisoxazolidines, nitroisoxazolines, dinitropiperidones, dinitroaziridines), tetranitropropanes, and gem -dinitrocyclopropanes [3–9]. No data on reactions of oxiranes with polynitromethanes have been reported so far, although these reactions can be considered as a new method for generation of alkyl nitronates, which are precursors of diverse heterocycles, and as a possible approach to the synthesis of trinitroalkanols. The trinitromethyl anion is known to show ambident properties, functioning as either an Oor a C-nucleophile depending on the substrate nature [1, 4, 7]. We suggested two possible pathways for its reaction with epoxides (Scheme 1), namely, pathway A including C-alkylation of the oxonium cation I to give 3,3,3-trinitropropanols II (two-component reaction) and pathway B including O-alkylation of the oxonium cation I with generation of an unstable nitronic ester III, which can either decompose to α -hydroxy ketone IV or undergo [3+2]-cycloaddition in the presence of an olefin to give 3,3-dinitroisoxazolidines V (three-component reaction).

Cyclic nitronic esters from highly diastereo-selective cycloaddition of 2-(4-morpholinyl)-norbornene to conjugated nitroolefins

The reactions of the morpholino enamine of 2-norbornanone towards a series of cyclic and acyclic conjugated nitroolefins resulted in the formation of the corresponding 1,2-oxazine N- oxides through an exo approach of the electrophiles. The stability of the heterocycles was strongly influenced by the nature of the substituents and in some cases it has been found to be unexpectedly high. Differently from analogous systems, opening of the heterocyclic ring to the corresponding enamine systems was not observed.

Studies on the chemistry of sodium nitronates and nitronic esters derived from 5-glyco-4-nitro-1-cyclohexenes

Reactions of sodium nitronates derived from 5-glyco-4-nitro-1-cyclohexenes with d- galacto or d- manno sugar side-chains have been investigated. With acetic anhydride/pyridine, these salts suffered an intramolecular cyclization affording high yields of tetraacetylated isoxazoline N-oxides. Treatment of the latter compounds with sodium methoxide yielded, either the corresponding deacetylated derivative or a bicyclic oxime, depending on the configuration of the sugar side-chain. Furthermore, unstable nitronic acid 13 has been isolated by recrystallization of nitronate 10 in dimethylsulfoxide, as well as by reaction of this substance with cold aqueous sulfuric acid. By refluxing with trimethyl phosphite, the N-oxides 14 and 16 led to isoxazolines which, like their precursors, could be considered as acyclic C-nucleosides.

Unexpected transformations: from 5-glyco-4-nitrocyclohexenes to bicyclic [3.3.1] oximes through isoxazoline N-oxides

Treatment of 5-glyco-4-nitrocyclohexenes with excess or equimolar sodium methoxide gave deacetylated sodium nitronates which, on reaction with Ac 2O/py, led to chiral isoxazoline N-oxides (cyclic nitronic esters). Depending on the configuration of their respective sugar side-chains, base-catalyzed deacetylation of these nitronate esters yielded either a bicyclic [3.3.1] oxime or a deacetylated isoxazoline N-oxide.

Correlation between structure and stability of nitronic acids and nitronic esters

Correlation between structure and stability of nitronic acids and nitronic esters

Correlation between structure and stability of nitronic acids and nitronic esters

On the basis of investigation on structural characteristics and stability of more than one hundred nitronic acids and nitronic esters, an equilibrium theory of electronic effects in conjugated systems is put forward and the type of structures is classified. On that basis, an empirical rule for the correlation between structure and stability of nitronic acids and nitronic esters is proposed, which predicts that stable nitronic acids and nitronic esters should have the C type of structure that meets the matching principle of electronic effects.

Studies on the chemistry of the chiral nitronic acid and nitronic esters

Some new chemistry of the chiral nitronic acid and nitronic esters is described. Conversions with retention of configuration are found among the chiral nitronic acid, oxime, nitronic esters and O-alkyloximes. α,β-Elimination reactions of nitronic esters are observed for the first time. Novel and enantiopure chiral bisheterocyclic compounds are obtained via highly diastereoselective 1,3-dipolar cycloaddition of the chiral nitronic esters with ethyl acrylate.

O- and C-alkylations of ethyl nitroacetate with benzyl halides

THE chemistry of nitronic esters remains relatively unknown due to their conspicuous feature ofinstability. In the preceding papers, we described the late progress in the researchof nitronic esters: (i) nitronic esters were first synthesized via O-alkylation of the alkali met-...

Synthesis and Characterization of Chiral Nitronic Esters via O-Alkylation of (4S*,5R)-(+)-4-(1‘-Nitro-1‘-carbethoxymethyl)- 5-[(1R)-menthyloxy]-3,4-dihydro-2(5H)-furanone with Alkyl Halides

A series of stable and enantiomerically pure alkyl nitronic esters are synthesized in good to excellent yields via O-alkylation of (4S*,5R)-(+)-4-(1‘-nitro-1‘-carbethoxymethyl)-5-[(1R)-menthyloxy]-3,4-dihydro-2(5H)-furanone (4a) with alkyl halides in the presence of K2CO3 and DMF at room temperature. Thus, nitronic esters are obtained for the first time from the alkali metal salt of a nitro compound and various alkyl halides, which refutes the traditionally held view that the reaction of alkyl halides with alkali metal derivatives of nitro compounds gives a carbonyl compound and an oxime, rather than a nitronic ester. Secondary alkyl nitronic esters are found to partially decompose into O-alkyloximes. The configurations of the nitronic esters and O-alkyloximes were assigned to be Z on the basis of the NOE experiments. The synthesis of the nitro furanone 4a and its enolization to form a six-membered intramolecular hydrogen bond structure are described.

Effect of the α-Alkyl Substituent of Conjugated Nitroolefins on the Formation of Cyclic Nitronic Esters vs. Nitrocyclopropanes in Their Reaction With Sulfur Ylides

The formation of cyclic nitronic esters (isoxazoline N-oxides) vs. nitrocyclopropanes in the reaction of conjugated nitroolefins with sulfur ylides depends on the presence of an α-alkyl substituent in the conjugated nitroolefins.

Photochemical Nitration by Tetranitromethane. XXIX. Adduct Formation in the Photochemical Reaction of Tetranitromethane and 1,5-Dimethylnaphthalene; Allylic Rearrangements of Adducts

Photolysis of the 1,5-dimethylnaphthalene/tetranitromethane charge-transfer complex yields the triad of 1,5-dimethylnaphthalene radical cation, nitrogen dioxide and trinitromethanide ion. Recombination of this triad gives predominantly the epimeric 4,8-dimethyl-1-nitro-4-trinitromethyl-1,4-dihydronaphthalenes (18) and (27), the epimeric 1,5-dimethyl-1-nitro-4-trinitromethyl-1,4-dihydronaphthalenes (20) and (21), 4,8-dimethyl-r-1-nitro-t-2-trinitromethyl-1,2-dihydronaphthalene (19), 4,8-dimethyl-t-2-trinitromethyl-1,2-dihydronaph-thalen-r-1-ol (23), nitro cycloadduct (22), hydroxy cycloadduct (24), nitronic ester (25) and 4,8-dimethyl-1-nitronaphthalene (26). Adduct (19) is formed substantially by allylic rearrangement of 4,8-dimethyl-1-nitro-4-trinitromethyl-1,4-dihydronaphthalene (18), and adduct (23) and indirectly nitronic ester (25) by allylic rearrangement of a postulated intermediate 4,8-dimethyl-t-4-trinitromethyl-1,4-dihydronaphthalen-r-1-ol (32). Adducts (18), (19), (23), (25) and (27) are formed by attack of trinitromethanide ion at C 1 of the 1,5-dimethylnaphthalene radical cation, while adducts (20)-(22) and (24) are formed by the corresponding attack at C4, the reaction pathways being determined by the relative energies of the intermediate delocalized carbon radicals. Adduct formation is substantially suppressed for a photolysis when trifluoroacetic acid (0.7 M) is added to the dichloromethane solvent at 20°, 1,5-dimethyl-4-nitronaphthalene (26) being formed close to quantitatively. In contrast, photolysis of the 1,5-dimethylnaphthalene/tetranitromethane charge-transfer complex in 1,1,1,3,3,3-hexafluoropropan-2-ol gave substantial amounts of adduct (19), together with 1,5-dimethyl-4-nitronaphthalene (26) as the major product. Allylic rearrangements of 1-methoxy-4-nitro-1-trinitromethyl-1,4-dihydronaphthalene (34) and the epimeric 1,4,5,8-tetramethyl-1-nitro-4-trinitromethyl-1,4-dihydronaphthalenes (38) are seen as the mode of formation of 4-methoxy-r-1-nitro-t-2-trinitromethyl-1,2-dihydronaphthalene (33) and the epimeric 1,4,5,8-tetramethyl-1-nitro-2-trinitromethyl-1,2-dihydronaphthalenes (36), respectively. X-Ray crystal structure determinations are reported for adducts (19), (20), (22), (24) and (28), the last compound being formed only on chromatography of reaction mixtures.