Aldehydes reactions with nitroacetic

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

The nitroaldol reaction of methyl nitroacetate (199, Scheme 38) with 1,2 3,4-di-0-isopropylidene-a-D-ga/acfo-hexodialdo-l,5-pyranose (200) and 2,3-O-isopropyli-dene-D-glyceraldehyde (202) catalyzed by silica gel proceeded in almost quantitative yield, with high selectivity for attack on the aldehyde carbonyl group, giving derivatives 201 and 203, respectively. Two of the four possible diastereomers were detected as main products, and were obtained as a mixture. For the nitroaldol reaction with 200 gave similar results in either the presence or absence of silica gel, whereas the reaction with 202 did not proceed in its absence, showing that catalytic action of silica is mandatory in this case.176... 

Microwave-assisted Knoevenagel reactions have also been used for preparation of resin-bound nitroalkenes [56]. A variety of resin-bound nitroalkenes has been generated by use of resin-bound nitroacetic acid, which was condensed with a variety of aldehydes under microwave conditions. To demonstrate the potential of these resin-bound products in combinatorial applications, the readily prepared nitroalkenes were subsequently employed in Diels-Alder reactions with 2,3-dimethylbutadiene [56]. 

Reactions of nitroacetic acid ester with aldehydes ... 

Substitutedisoxazole-3,5-dicarboxylic acids have been prepared from ethyl nitroacetate and an aldehyde (63BCJii50). A related reaction leads to diethyl 4-hydroxyisoxazole-3,5-dicarboxylate (334) and involves the reaction of acetonedicarboxylic acid ester (333) with nitrosyl chloride (78JHC1519). 

Aluminum oxide catalyzed addition of ethyl nitroacetate to racemic 2,3-cpoxy aldehydes 7 affords substituted 4,5-dihydroisoxazole 2-oxides through a regio- and stereospecific tandem nitroaldol cyclization process. High diastereoselectivities are observed in the reaction of cis-epoxyaldehydes to yield the ethyl, vi7 -4.5-dihydro-4-hydroxy-5-( I -hydroxyalkyl)-3-isoxazole-carboxylate 2-oxides, with tram configuration at the ring positions, whereas reactions of trans-and 3,3-disubstituted 2,3-epoxyaldehydes proceed with lower selectivities28. 

Reactions of methyl nitroacetate with aldehydes are induced by TiCl4 in pyridine. They afford nitroalkenyl-esters,64 which are used in the preparation of various nonnatural amino acids (Eq. 3.39).65... 

Curiously, however, reaction of the dialdehyde (94b) with ethyl nitroacetate under practically identical conditions — aqueous ethanol in the presence of sodium acetate and sodium carbonate at pH 8.6 — takes a different course. The compound, isolated in 34% yield, constitutes a monoaddition product to one aldehyde group, as evidenced by the formation of a triacetate after hydrogenation and acetylation. It has been assigned structure (95) 5 ) and, as such, is a C-substituted derivative of the hemialdal form (94a) of the dialdehyde. Though some NMR data were cited as proof of this formulation 58) two alternatives, (96) and (97) respectively, cannot be ruled out. Of these, structure (97) derived from... 

Reaction at the C atom of nitronate salts is known with a variety of electrophiles, such as aldehydes (Henry reaction) and epoxides (191-193). Thus the incorporation of the nitro moiety and the cyclization event can be combined into a tandem sequence. Addition of the potassium salt of dinitromethane to an a-haloaldehyde affords a nitro aldol product that can then undergo intramolecular O-alkylation to provide the cyclic nitronate (208, Eq. 2.17) (59). This process also has been expanded to a-nitroacetates and unfunctionalized nitroalkanes. Other electrophiles include functionalized a-haloaldehydes (194,195), a-epoxyaldehydes (196), a-haloenones (60), and a-halosulfonium salts (197), (Chart 2.2). In the case of unsubstituted enones, it is reported that the intermediate nitronate salt can undergo formation of a hemiacetal, which can be acetylated in moderate yield (198). 

Most C,H-acidic compounds can be condensed with aldehydes or ketones to yield alkenes. Some of these reactions have also been realized on insoluble supports, with either the C,H-acidic (nucleophilic) reactant or the electrophilic reactant linked to the support. Some illustrative examples are listed in Table 5.6. Polystyrene-bound malonic esters or amides, cyanoacetamides, nitroacetic ester [95], and 3-oxo esters undergo Knoevenagel condensation with aromatic or aliphatic aldehydes. Catalytic amounts of piperidine and heating are generally required, although reactive substrates can react at room temperature. 

Reactions of carbonyl compounds with nitroalkanes like nitromethane (Henry reaction) are described in Volume 2, Chapter 1.10. The doubly activated ethyl nitroacetate readily reacts with aliphatic, aromatic and heteroaromatic aldehydes to give a,p-unsaturated-a-nitrocarboxylic acid esters in the presence of TiCU/V-methylmorpholine as mixtures of cis and trans isomers. ... 

Thiophen-2-aldehyde has been used in a preparatively useful modification of the Knoevenagel reaction in which TiCU and a tertiary amine in tetrahydrofuran were used in order to achieve facile condensation with ethyl acetoacetate and ethyl nitroacetate. The reaction of the dibromo-derivative (155) obtained from the corresponding chalcone with cyclo-hexylamine gave the 2-(2-thienyl)aziridine (156). The reaction of (156)... 

The reaction of alcohols with ethyl nitroacetate, diethyl azodicarboxylate, and triphenylphosphine gives aldehydes or ketones via their aci-nitroesters. ... 

Synthesis of 159 An ordinary vial equipped with a magnetic stirring bar was charged with aldehyde 155 (0.2 mmol, 1 equiv), catalyst 157 (0.04 mmol, 0.2 equiv), benzoic acid (0.04 mmol, 0.2 equiv), H2O (0.2 mmol, 1 equiv), and dichloromethane (0.8 mL). The mixture was cooled to 20 C, and the electrophile 156 (0.3 mmol, 1.5 equiv) was added. Stirring was continued at this temperature for 90 minutes, at which point the nitroacetate (0.26 mmol, 1.3 equiv) and imidazole (0.66 mmol, 3.3 equiv) were added. After a further 16 hours of stirring at —20 C, the crude reaction mixture was directly charged on silica gel and subjected to flash column chromatography. 

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