Alkyl nitronates acylation

Stability of Acyclic Alkyl and Acyl Nitronates A weak point of acyclic alkyl nitronates is their thermal instability because these compounds can be involved in two electrocyclic reactions presented in Scheme 3.72. 

The reactions of alkyl nitronates (164) or (165) derived from a-functionalized primary AN with monosubstituted acetylenes produce mixtures of diastereomeric aziridines (166) in moderate to high yields. Most probably, the first step of this process involves normal concerted cycloaddition to give the corresponding intermediates A, which were not detected due to their fast rearrangement to give acyl-substituted aziridines (166). The reaction is regioselective and stereospecific. The latter fact was demonstrated by French researchers (95). 

The 1,2,4-diazaarsoles are colorless oils or crystals. The unsubstituted compound is deprotonated by butyllithium and subsequently alkylated or acylated at N-1 <86TL2957>. The 1-acyl derivatives (9) (R = Me, Ph) readily undergo a regiospecific cycloaddition of nitrones, nitrile oxides and diazoacetic esters (Scheme 1). The cycloaddition of diphenyl nitrile imine is more general in respect to the 1-substituent (R = H, Me, Ph, COMe). The cycloreversion of the adduct (10) at higher temperatures provides an in situ access to the 1,3-diphenyl diazaarsole (11) which immediately enters another cycloaddition (Scheme 2) <86TL2957>. 

The commonly accepted mechanism for these isoxazole syntheses assumes the formation of intermediate mixed anhydrides between nitronic acid 6a and the acyl moiety. Many authors have illustrated these intermediates 6b (Scheme 8.2) where the acyl group (X = acyl) in turn is PhNHCO [5], MeCO [31,32,47,48], t-BuCO [32], t-BuOCO [42], EtOCO [37], PhCHaOCO [32], ArCO [32], PhSOa [37], p-TsO [36]. These nitronic mixed anhydrides are intermediates that usually carmot be isolated, unlike die esters alkyl nitronates 6c and silylnitronates 6d (Scheme 8.2). These esters 6c [49,50] and 6d [51-54] behave as 1,3-dipoles toward suitable dipolarophiles, and the resulting cycloadducts 7c and 7d are then converted into the final isoxazole derivatives by elimination of alcohol or silanol respectively in these cases cycloadditions precede elimination. 

The reaction is versatile and proceeds with a variety of cyclic and acylic alkenes substituted with alkyl, aryl, vinyl and heteroatom substituents. Allene derivatives also undergo cycloaddition with nitrones ". A variety of cyclic and acyclic aliphatic nitrones bearing aliphatic and aromatic substituents has been tested. The reaction is, however, relatively sensitive to steric constraints and proceeds easily only for mono- and disubstituted alkenes. Steric requirements for a nitrone molecule are similar and, although several reactions with R, R2 are known, good yield has been achieved only with R = H (equation 105). 

The X-ray crystallographic data for an acyl nitronate (25) is compiled in Table 2.14 (56). Because the phenyl group attached to the nitronate, the bond angles about the sp hybridized nitrogen are similar to those of nitronates 9 and 10. However, the 0(1)—N bond is slightly shorter than those in either the alkyl or silyl nitronates, while the 0(2)—N is slightly longer. This is in line with the observed instability of monosubstituted acyl nitronates, which eliminate readily to the nitrile oxides. 

The versatility of 5-nitrosopyrimidines in pteridine syntheses was noticed by Pachter (64MI21603) during modification of the Timmis condensation between (262) and benzyl methyl ketone simple condensation leads to 4-amino-7-methyl-2,6-diphenylpteridine (264) but in the presence of cyanide ion 4,7-diamino-2,6-diphenylpteridine (265) is formed (equation 90). The mechanism of this reaction is still uncertain (63JOC1187) it may involve an oxidation of an intermediate hydroxylamine derivative, nitrone formation similar to the Krohnke reaction, or nucleophilic addition of the cyanide ion to the Schiff s base function (266) followed by cyclization to a 7-amino-5,6-dihydropteridine derivative (267), oxidation to a quinonoid-type product (268) and loss of the acyl group (equation 91). Extension of these principles to a-aryl- and a-alkyl-acetoacetonitriles omits the oxidation step and gives higher yields, and forms 6-alkyl-7-aminopteridines, which cannot be obtained directly from simple aliphatic ketones. 

The H-NMR data indicated that C-aryl-/V-(2-carboxyalkyl)nitrones exist only as the open-chain isomers 41A in solution. However, in acylation reactions, they formed 0-acyl derivatives with the cyclic structure, whereas alkylation with phenacyl bromide led to the open-chain esters (84LA1545). 

Reductions. Nitrones and N-oxides are deoxygenated by (BnNEtjljMoS. Acyl azides give amides. Alkyl azides undergo a homocoupling reaction to form imines, whereas stabilized azides, such as acyl, sulfonyl, and aryl azides, undergo reductive elimination of... 

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