Nitromethane, enolate anion

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. 

It is known that acetone enolate anion does not react with primary alkyl radicals, and that nitromethane anion is not capable of initiating the SRN1 reactions even under irradiation [99]. Thus, the photo stimulated reactions of 25 with nitromethane anion as nucleophile and acetone enolate anion as entrainment reagent (which enables SRN1 initiation but cannot compete with the coupling of the methylene radical with nitromethane anion after cyclization) render the cyclized products 26 (Sch. 25) [98]. 

The palladium catalyst generally used is Pd(PPhj)4, which can be formed in situ from Pd(OAc)2 and PPhj. The most often used allylic substrates are those having an ester or a carbonate as a leaving group, although -OPO(OR)2, -OPh, -Cl, or -Br will also work. Soft nucleophiles of the malonate-type generally give the best results for carbon-carbon bond formation. The reaction is usually in eversible and thus proceeds under kinetic control. Other soft carbon nucleophiles are anions from nitromethane, enolates, and enamines. 

Chain-lengthening reactions can be applied to carbohydrates. As the term implies, the carbohydrate chain is extended by one carbon. One important method uses a transformation called the Nef reaction, after John U. Nef (Switzerland/ United States 1862-1915). When d-threose (13) reacts with nitromethane in the presence of sodium methoxide as a base, the enolate anion of nitromethane (90) reacts with the aldehyde unit of 13 (an enolate-aldehyde condensation reaction see Chapter 22, Section 22.2, for related reactions) to give two products 91 and 92. 

Acetophenone enolate and nitromethane anions have also been used successfully in alkyl substitution. 

Acyl imidazolides are more reactive than esters but not as reactive as acyl halides. Entry 7 is an example of formation of a (3-ketoesters by reaction of magnesium enolate monoalkyl malonate ester by an imidazolide. Acyl imidazolides also are used for acylation of ester enolates and nitromethane anion, as illustrated by Entries 8, 9, and 10. (V-Methoxy-lV-methylamides are also useful for acylation of ester enolates. 

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... 

Acyl imidazolides have also been used for acylation of ester enolates and nitromethane anion, as illustrated by entries 9 and 10 in Scheme 2.14. 

The reactions of 1,3-dihaloadamantanes with various carbanions in DMSO have been studied.18 For example, potassium enolates of acetophenone and pinacolone and the anion of nitromethane react with 1,3-diiodoadamantane (19) under photo-stimulation a free-radical chain process forms a 1-iodo monosubstitution product (20) as an intermediate, which undergoes concerted fragmentation to yield derivatives of 7-methylidenebicyclo[3.3.1]nonene (21). These and other results were interpreted in terms of the Srn1 mechanism. The work has been extended to the reactions of 1- and 2-halo- and 1,2-dichloro-adamantanes, examples of the SrnI mechanism again being found.19... 

Photostimulated, S r k 1 reactions of carbanion nucleophiles in DMSO have been used to advantage in C—C bond formation (Scheme 1).25-27 Thus, good yields of substitution products have been obtained from neopentyl iodide on reaction with enolates of acetophenone and anthrone, but not with the conjugate base of acetone or nitromethane (unless used in conjunction, whereby the former acts as an entrainment agent).25 1,3-Diiodoadamantane forms an intermediate 1-iodo mono substitution product on reaction with potassium enolates of acetophenone and pinacolone and with the anion of nitromethane subsequent fragmentation of the intermediate gives derivatives of 7-methylidenebicyclo[3.3.1]nonene. Reactions of 1,3-dibromo- and 1-bromo-3-chloro-adamantane are less effective.26... 

The enantio-determining step of nucleophilic additions to a-bromo-a,y -unsaturated ketones is mechanistically similar to those of nucleophilic epoxidations of enones, and asymmetry has also been induced in these processes using chiral phase-transfer catalysts [20]. The addition of the enolate of benzyl a-cyanoacetate to the enone 31, catalysed by the chiral ammonium salt 32, was highly diastereoselective and gave the cyclopropane 33 in 83% ee (Scheme 12). Good enantiomeric excesses have also been observed in reactions involving the anions of nitromethane and an a-cyanosulfone [20]. 

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]. 

Nitromethane anion (31) failed to initiate the reaction with 97. However, when the reaction was performed in the presence of the enolate ion of the acetone (27a) as initiator, the corresponding substitution product 105 was the only product formed in 69% yield (equation 77)157. 

The anion of nitromethane (31) failed to react with Phi under irradiation in DMSO, as was the case with 1-AdI. However, when the reaction was carried out in the presence of acetone (27a) or pinacolone (27b) enolate ions, l-phenyl-2-nitroethane (161) was formed as major product, together with small amounts of benzene and toluene (equation 104). No products from the coupling with the ketone enolate ions were found169... 

Aliphatic nitro compounds show a number of reactions which parallel those of carbonyl chemistry. Primary and secondary nitro compounds exhibit tautomerism paralleling keto-enol tautomerism (Scheme 3.94a). Aliphatic nitro compounds dissolve in aqueous sodium hydroxide with the formation of sodium salts. The resultant anions behave as carban-ions and will condense with aldehydes. An example involves the formation of m-nitrostyrene from nitromethane and benzaldehyde (Scheme 3.94b). 

Nitroalkanes form enolate-like anions in quite weak base. As in base-catalysed enolization, a proton is removed from a carbon atom and a stable oxyanion is formed, nitromethane formation of nitromethane anion in base... 

We can complement this type of selectivity with the opposite type. Are there any compounds that can enolize but that cannot function as electrophiles No carbonyl compound can fill this role, but in Chapter 21 we met some enolizable compounds that lacked carbonyl groups altogether. Most notable among these were the nitroalkanes. Deprotonation of nitroalkanes is not enolization nor is the product an enolate ion, but the whole thing is so similar to enolization that it makes sense to consider them together. The anions, sometimes called nitronates, react well with aldehydes and ketones, anion of nitromethane... 

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. 

A similar situation arises in all cases of this kind. Protonation of such ambident anions on nitrogen or oxygen is always much faster than protonation on carbon. Under kinetic control, the product is therefore invariably an enol or analog of an enol, e.g., the aci isomer CH2=NOOH in the case of the conjugate base (CH2 N02) from nitromethane. At equilibrium, i.e., under thermodynamic control, the more stable isomer is favored. In the case of simple ketones, this is the ketonic isomer. However, in the case of dimethyl oxaloacetate (14), the enol is the more stable form in ethanolic solution and it is therefore almost the sole product under conditions either of kinetic control or thermodynamic control. ... 

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