Nitroketones

Alkali salts of primary nitroparaffins, but not of secondary nitroparaffins, react with acyl cyanides to yield a-nitroketones by C-acylation (27). 

A number of reductive procedures have found general applicability. a-Azidoketones may be reduced catalytically to the dihydropyrazines (80OPP265) and a direct conversion of a-azidoketones to pyrazines by treatment with triphenylphosphine in benzene (Scheme 55) has been reported to proceed in moderate to good yields (69LA(727)23l). Similarly, a-nitroketones may be reduced to the a-aminoketones which dimerize spontaneously (69USP3453279). The products from this reaction are pyrazines and piperazines and an intermolecular redox reaction between the initially formed dihydropyrazines may explain their formation. Normally, if the reaction is carried out in aqueous acetic acid the pyrazine predominates, but in less polar solvents over-reduction results in extensive piperazine formation. 

This class was first reported in 1924 and was formed 62HC(17)l) by cyclization of a-bromo-/3-aryl-y-nitroketones. The direct synthesis by oxygenation of 2-isoxazolines has not been reported. To date only 3-substituted derivatives have been prepared. Aryl-nitromethanes react with nitrostilbene to form isoxazoline A-oxide by a nitrile ion displacement (Scheme 138) <62HC(17)1, 68TL3375). 

A particular case of the synthesis of isoxazoles via -diketone derivatives is the preparation of 3-halogenoisoxazoles (11) from -nitroketones (9) treated with hydrogen halides. This inter-... 

Valendn and coworkers have studied extensively the reaction of enamines v/ith nltroalkenes. The reaction proceeds under rruld conditions to give y-nitroketones, which are converted into 1,4-diketones by the Nef reaction CEq. 4.65. ... 

One-pot syntheses of 1,4-diketones, yoxoaldehydes, yketoesters, and oj-oxoalkanoates have been reported by bond cleavage of cyclic ct-nitroketones v/ith KOH in methanol and subsequent Nef reacdon fSecdon d.l with KMnOi) fEq. 5.16. ... 

Recently, Narasaka and co-workers have found that Tnitroalkyl radicals are generated by oxidadon of nci-nitroanions vrith CAN, and they undergo the intermolecidar addidon to electron-rich olefins. For example, when oxidadon is carried out in the presence of silylenol ethers, fi-nitroketones are formed in good yield. fi-Nitroketones are readily converted into u vrith base ("see Secdon 7.3, as shovm in Eq. 5.43. 

The reduction of y-nitroketone acetals as in Eq. 6.50 v/ith ammonium formate in the presence of Pd/C gives the correspondmg amines in good yields. However, the reduction ofy-nitro ketones are reduced to cyclic nitrones fEq. 6.51. This reduction is far superior to the classical method using Zn/T4HlCl due to improved yield and simple workup. 

The high acidity of ct-nitroketones makes it possible to perform the Henry reacdons or Michael addidons under extremely rruld condidons The reacdon proceeds in the presence of catalydc amounts of Ph-vP to give the C-C bond formadon products under nearly neutral condidons Thus, 1,5-dicarbonyl compounds and ct-methylenecarbonyl compounds are prepared by the denitradon of ct-nitroketones, as shown in Eqs 7 67 and 7 68, respecdvely... 

The simidtaneous denitradon-deoxygenadon of ct-nitroketones is performed o withTsNUNHj and NaBbb, at 80 C to give alkanes fEq 7 90 ... 

Redncdons of y-nitroketones yield cyclic nitrones, which undergo inter- and intramolecular cycloadthdon to various alkenes. The result of adthdon to acrylonitrile is shown in Eq. 8.43, in which a rruxnire of regio- and stereoisomers is formed. - ... 

The Michael dclclidon of nitro ilkdnes to a,fi-unsdnirdted ketones gives Y-nitroketones, which re convetted into pyrroles by reduction of the nitro group with and PhSSPh fEq. 10.2. ... 

As a new and practical synthesis of pyrroles, Zard and coworkers have presented the reduction of Y-nitroketones v/ith formamidinesiilfinic acid fEq. IC.Bi/... 

Ruthenium complex catMyzes reducdve iV-heterocyclizadon of y-nitroketones to give pyr-rohne detivadves fEq. 10.72. ... 

Baker s yeast reducdon of y-nitroketones offers the corresponding chiral nitro alcohols, which areusefid bndding blocks for the synthesis of chiral naniral compounds. For example, opdcally acdve 2-subsdnited pyrrolidine can be prepared using the chiral nitro alcohol fEq. 10.751. ... 

The enandoselecdve reducdon ofy-nitroketones andy-nitrodiketones by the chiral reducing agent f+ - or f- -diisopinocamphenylchloroboranerDIP-Cl gives nitro alcohols having from 33 to 86% ee and nitrodiols v/ith complete diastereoselecdvity and > 95% ee. 

In the aliphatic series, hydrogenation of y-nitroketones gives pyrrolidines in good yields (52) and tx-nitroketones give a mixture of pyrazines and piperazines (i5). 

Rovis and co-workers have also extended the intermolecular Stetter reaction to inclnde nitroaUcenes as the electrophilic component. Fluorinated triazolinm precatalyst 155 was effective in catalysing the reaction of a variety of heteroaromatic aldehydes 153 with nitroalkenes 154 to generate P-nitroketones in excellent yields and enantioselectivities. The authors propose that stereoelectronically induced conformational effects on the catalyst skeleton are key to the high selectivities observed with flnorinated catalyst 155 (Scheme 12.33) [69],... 

Nitroacetone (237 g) was generated in dichloromethane-ethyl acetate solution by treating its dicyclohexylamine aci-salt with sulfuric acid. Towards the end of concentration of the solution by rotary vacuum evaporation at 40-50°C, a small explosion occurred. Extreme caution and small scale handling of a-nitroketones are urged [1], If exact neutralisation of the dicyclohexylamine salt had not been achieved, presence of excess sulfuric acid (or of some undecomposed aci-salt) may have reduced the stability of the nitroacetone [2],... 

Enantioselective allylations of a-nitro ketones and a-nitro esters with allyl acetates are carried out in the presence of 2 equiv of alkali metal fluorides (KF, RbF, CsF) and 1 mol% palladium catalysts prepared in situ from Pd2(dba)3-CHC13 and chiral phosphine ligands. Moderate enantio-selectivity (ca 50% ee) is reported for allylation of cx-nitroketones (Eq. 5.60). The highest selectivity (80% ee) is observed for allylation of the reaction of tert-butyl ester (Eq. 5.61).93... 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

Although this method is not a general procedure, being specific for a-nitroketones, it has several merits to avoid the use of toxic reagents such as organotin compounds. Functionalized ketones have been prepared by this denitration reaction, in which functionalized nitroalkanes are used as alkyl anion synthons. For example, 3-nitropropanal ethylene acetal can be used as synthon of the 3-oxo-propyl anion and 1,4-dicarbonyl compounds are prepared, as shown in Eq. 7.88.135... 

The simultaneous denitration-deoxygenation of a-nitroketones is performed on treatment with TsNHNH2 and NaBH4 at 80 °C to give alkanes (Eq. 7.90).137... 

Finally, trialkyl-substituted pyrazines 104 were prepared in a regiocontrolled manner from -nitroketones by reaction with -amino ketones <05OL5529>. 

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