Nitronate ester

A second and related consequence in aliphatic nitro compounds is the acidification of the directly bonded CH unit through the attendant stabilization of the derived conjugate bases (5,6). As with all delocalized anions, reprotonation gives rise to tautomers, the original C-nitro compound (I) and the oci-nitro or isonitro form (II), Eq. 2.1. The aci-nitro tautomers are typically present in very minor concentrations, with equilibrium constants (A eq) between 10 and 10 (7). Alkylation of the delocalized anion leads to both a-substituted nitro compounds and the regioisomeric nitronic esters (nitronates). Nitronates were described as early as 1894 (8), however, the first isolated nitronic ester was obtained several years later upon the addition of diazomethane to phenylazonitromethane (1), Eq. 2.2 (9). 

Addition to C=N. Chiral amines are synthesized by Grignard reaction of f-butanesulfinamdes. ° An access to p-branched a-amino acids involves addition of RMgX to 2W-azirene-2-carboxylic esters." Nitrones derived from serine and chiral ot-amino aldehydes (thence the amino acids) are sources of a,P-diamino acids and 1,2-diamines, respectively. 

EINECS 246-363-6 Ethylhexyl nitrate 2-Ethylhexyl nitrate Exchem GO-1 Nitric acid, 2-ethyihexyl ester Nitronal. 

Similarly, oxazolidine (13) was obtained from A -pyrroline N-oxide (12) and methyl but-3-enoate, by ( cloaddition (90% yield). m-Chloroperbenzoic acid (MCBA) converted the adduct into the ester nitrone (14). The latter, as an adduct... 

Aminohydroperoxides Aminoxycarbonyl Hydroxamic acid esters Hydroximic acids Iminocarbonic acid esters Nitronic —... 

The Kanemasa group utilized the strategy of 13DC of electron deficient activated ester nitronates 172 and 175 arising from dimethyl nitromalonate and methyl nitroacetate, respectively, with the magnesium derivative of al-lylic alcohols 173 for the synthesis of substituted isoxazolines 174 and 176 (Scheme 44) [145]. The monoester nitronate 175 was originally an E Z mixture in 1 1.8 ratio. 

Carbarn ic acid silyl esters Nitronic acid silyl esters N-Silylurethans... 

Iminocarbonic acid esters Nitronic acid esters... 

Entry Alkenylboronic ester Nitrone Isolated yield (%)... 

Hydroxamic acids and esters Hydroximic acids and esters Iminocarbonic acid esters Nitronic — O-Alkylnitronates 20 Nitronates 20 Urethans... 

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

Nitrones or aci-nitro esters react with alkenes to give in some cases A/-substituted isoxazolidines and in others 2-isoxazolines. When the intermediate isoxazolidines were observed, a number of procedures transformed them into the 2-isoxazolines. Acrylonitrile and phenyl rzcf-nitrone esters produced an A/-methoxyisoxazolidine. Treatment with acid generated a 2-isoxazole while treatment with base generated an oxazine (Scheme 118) (68ZOR236). When an ethoxycarbonyl nitrone ester was reacted with alkenes, no intermediate isoxazolidine was observed, only A -isoxazolines. Other aci-mtro methyl esters used are shown in Scheme 118 and these generate IV-methoxyisoxazolidines or A -isoxazolines which can be further transformed (72MI41605). 

The addition of nitronic esters to alkynes to produce aziridines was postulated to proceed through a 4-isoxazoline as one of the intermediates (Scheme 132). A biradical intermediate (492) was also included in the mechanistic pathway for the reaction (77JA6667). 

A newer method for the preparation of nitronic esters, namely utilizing the (9-trimethyl-silyl ester, has been reported and these are prepared by the reaction of alkylnitro compounds and (V,(V-bis(trimethylsilyl)acetamide. These nitronic esters also undergo cycloaddition with alkenes to produce isoxazolidines (equation 54) (74MIP41601, 74DOK109, 78ACS(B)ll8). 

Steroidal alkene (531a) reacted with a nitronic ester at 14 000 atmospheres to produce an isoxazolidine (532a) (80IZV1893). 

A" -Isoxazolines, which are readily accessible by 1,3-dipolar addition of nitrones and nitronic esters to activated alkynes, undergo facile rearrangement upon warming (<110 °C)... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

The enantioselective inverse electron-demand 1,3-dipolar cycloaddition reactions of nitrones with alkenes described so far were catalyzed by metal complexes that favor a monodentate coordination of the nitrone, such as boron and aluminum complexes. However, the glyoxylate-derived nitrone 36 favors a bidentate coordination to the catalyst. This nitrone is a very interesting substrate, since the products that are obtained from the reaction with alkenes are masked a-amino acids. One of the characteristics of nitrones such as 36, having an ester moiety in the a position, is the swift E/Z equilibrium at room temperature (Scheme 6.28). In the crystalline form nitrone 36 exists as the pure Z isomer, however, in solution nitrone 36 have been shown to exists as a mixture of the E and Z isomers. This equilibrium could however be shifted to the Z isomer in the presence of a Lewis acid [74]. 

The required nitro compounds are easy to prepare, and are useful building blocks for synthesis. Treatment with an appropriate base—e.g. aqueous alkali—leads to formation of nitronates 2. Various substituted nitro compounds, such as nitro-ketones, -alcohols, -esters and -nitriles are suitable starting materials. 

Cycloaddidon of the cychc nitrone derived ftom prolide benzyl ester v/ith alkenes proceeds readily to give isoxazohdines v/ith good regio-and stereoselecdvity fEq 8 47i The reaction favors exo-mode addidon However, certin cycloaddidons are reversible and therefore the product distribndon may reflect thermodynamic rather than kinedc control... 

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