Bonding alkyl nitronates

Diazo compounds and oxonium salts are the most efficient alkylating agents in the synthesis of alkyl nitronates. It is assumed that diazo compounds are inserted into the O-H bond in the aci forms of the corresponding AN, whereas oxonium salts generally react with AN anions. 

As mentioned above (303) (Scheme 3.90, Eq. 1), bis-trifluoromethyl thioketene has the deoxygenating ability toward alkyl nitronates, which is also based on cycloaddition to the C=S bond. 

N—0(2) bonds are 1.274 and 1.424 A, respectively. The X-ray crystallographic data for 24 corresponds well with those of 22, however, the bond angles of 23 are drastically different from the other two alkyl nitronates. Interestingly, these bond angles agree better with those observed in the silyl nitronates, however, this may be due to the constraints imposed by the fused seven- and six-membered rings. 

Treatment of 2- 5//-dibenz[i>,/]azepin-5-yl acetaldehyde (16), prepared in 68% yield by /V-alkylation of 5/7-dibenz[A,/]azepine with bromoacetaldehyde diethyl acetal followed by acid hydrolysis, with methyl hydroxylamine yields the isolable nitrone 17, which in refluxing toluene undergoes intramolecular 1,3-dipolar cycloaddition at the CIO —Cl 1 alkene bond to give 2,3,3a, 12b-tetrahydro-2-methyl-3,8-methano-8//-dibenz[i>,/]isoxazolo[4,5-r/]azepine (18).235... 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

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). 

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. 

Treatment of sodium and potassium nitronates with alkyl halides typically results in the formation of oximes and carbonyl compounds by cleavage of the N—O bond (11). In one case, however, reaction of w-butyl bromide with the potassium salt of nitro ester 191 does afford the -butyl nitronate (192, Eq. 2.14) (154). 

In the synthesis of analogues of calicheamicin 71 and esperamicin Ajb, Moutel and Prandi employed the glycosyla-tion of a nitrone with a trichloroacetimidate as a key step - /3-N-O glycosidic bond formation. Preparation of the nitrone begins with the alkylation of the known alcohol 69 <1992CC1494> with 1,4-dibromobutane in the presence of sodium hydride. Subsequent aminoalkylation, amine protection with 9-fluorenylmethoxycarbonyl (Fmoc), and reduction with NaBHsCN were followed by nitrone 70 formation with 4-methoxybenzaldehyde (Scheme 8) <2001J(P1)305>. 

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