Anions nitro enolates

THF reduces aliphatic nitro enolate anions to hydroxylamines ... 

The nitro group can be converted into other useful functional groups following conjugate addition. Reduction gives primary amines while hydrolysis reveals ketones. The hydrolysis is known as the Nef reaction and used to be achieved by formation of the nitro-stabilized anion with a base such as sodium hydroxide followed by hydrolysis with sulfuric acid. These conditions are rather unforgiving for many substrates (and products) so milder methods have been developed. One of these involves ozonolysis of the nitro enolate at low temperature rather than treatment with acid. 

Another related method uses the anion of nitroalkanes in a reaction with halo-esters. Nitromethane reacted with lithium diisopropylamide to form the nitro enolate and then with methyl 3-chloropentanoatc to give 4.110. Reduction of the nitro group with ammonium formate gave methyl 2-phenyl-3-aminopropanoate, 4.111. 

Nitro groups attached to a primary and secondary alkyl group in a highly basic (pH > 13) medium exist as the nitronate (enolate) anions. These anions must be very difficult to reduce by electron transfer and are surely much more difficult to reduce than water. Since the electrohydrogenation of such nitro compounds to the corresponding amines is veiy efficient at Raney metal cathodes in 0.1 to 0.15 M KOH (or NaOH) aqueous alcohol (pH > 13) (12), as... 

The anion of nitromethane is particularly reactive in S l reactions. Various kinds of tertiary nitro groups are replaced by a nitromethyl group on treatment with the anion of nitromethane (Section 7.1).49 2-Iodoadamantane reacts with the anion of nitromethane in the presence of acetone enolate (entrainment reaction) under irradiation of a 400-W UV lamp to give 2-ni-tromethyladamantane in 68% yield, (see Eq. 5.32).50a 1-Iodoadamantane also reacts with the anion of nitromethane in a similar way.50b... 

Yosikoshi reported the synthesis of furan derivatives by the reaction of 1,3-diketones with nitroalkenes, in which the Michael addition of the anions of 1,3-diketones and the subsequent intramolecular displacement of the nitro group by enolate oxygen are involved as key steps (Eq. 7.40).42... 

The combination of silyl enol ethers and fluoride ion provides more reactive anions to give alkylated nitro compounds in good yields after oxidation with DDQ, as shown in Eq. 9.22.36 This process provides a new method for synthesis of indoles and oxyindoles (see Chapter 10, Synthesis of Heterocyclic Compounds). 

The existence of a protonated oxazolone has been demonstrated indirectly by a simple experiment. When p-nitrophenol was added to an excess of 2-alkoxy-5(4//)-oxazolone in dichloromethane, a yellow color appeared. The color persisted until all the p-nitrophenol had been consumed by the oxazolone. The anion of p-nitro-phenol is yellow. The explanation for the color of the mixture is the presence of the p-nitrophenoxide anion that was generated by abstraction of the proton by the oxazolone. In summary, protonation of the O-acylisourea suppresses the side reaction of oxazolone formation as well as the side reaction of A-acylurea formation and accelerates its consumption by enhancing its reactivity and generating an additional good nucleophile that consumes it. Protonation of the oxazolone suppresses epimerization by preventing its enolization and also increases the rate at which it is consumed.4 68 78 79... 

Accordingly, it is possible to generate analognes of enolate anions containing cyano and nitro groups, and to use these as nucleophiles towards carbonyl electrophiles in aldol-like processes. Simple examples are shown. 

The anion formed by removal of the 3-H is analogous to the enolate anion of Eq. 13-6 and has a strong structural similarity to the readily formed anions of organic nitro compounds. The nitronate anions may, perhaps, be regarded as transition state inhibitors. 

Many carbanionic nucleophiles that would be considered too hard to react as Michael donors can be made into effective reagents for conjugate addition reactions by appending resonance or inductively stabilizing groups to soften their intrinsic Lewis basicity. Such stabilized anionic Michael donors include enolates, alkylthio-substituted carbanions, ylides and nitro-substituted carbanions. 

Considerable use has also been made of allyl carbonates as substrates for the allylation of Pd enolates.9 The reaction of Pd° complexes with allyl enol carbonates119,120 proceeds by initial oxidative addition into the allylic C—O bond of the carbonate followed by decarboxylation, yielding an allylpalladium enolate, which subsequently produces Pd° and the allylated ketone (equation 22). In like fashion, except now in an intermolecular sense, allyl carbonates have been found to allylate enol silyl ethers (equation 23),121 enol acetates (with MeOSnBu3 as cocatalyst) (equation 24),122 ketene silyl acetals (equation 25)123 and anions a to nitro, cyano, sulfonyl and keto groups.115,124 In these cases, the alkoxy moiety liberated from the carbonate on decarboxylation serves as the key reagent in generating the Pd enolate. 

In chapter 21 we mentioned nitro compounds as promoters of conjugate addition they also stabilise anions strongly but do not usually act as electrophiles so that self-condensation is not found with nitro compounds. The nitro group is more than twice as good as a carbonyl group at stabilising an enolate anion. Nitromethane (p/ a 10) 1 has a lower pKa than malonates 4 (pKa 13). In fact it dissolves in aqueous NaOH as the enolate anion 3 formed in a way 2 that looks like enolate anion formation. 

Nitromethane anion gives the corresponding N-allyl-3-(2-nitro-ethyl)- 2,3-dihydro-1-H-indole in 60% yield after photostimulated reaction with the bromide analogue, and in the presence of the enolate ion and acetone as an entrainment reagent (Scheme 10.51) [67]. 

Because non-basic substances may also produce a similar reaction, it was later suggested by Anslow and King [66] that the enolate anion of creatinine forms a coordinate bond with the positively charged nitrogen atom of one of the nitro groups. The structure of the compound they postulated is VII ... 

The powerful electron-withdrawing nature of the nitro group means that deprotonation is possible even with very mild bases (the pkTa of MeNO is 10). The anions react with carbon electrophiles and a wide variety of nitro-containing products can be produced. The anions are not, of course, enolates, but replacing the nitrogen with a carbon should help you to recognize the close similarity of these alkylations with the enolate alkylations described later. 

The enolate ion intermediate is now much more basic than the anion of the nitro compound so it removes a proton from the nitro compound and provides another molecule of anion for the seeond round of the reaction,... 

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