Nitroalkanes stability

Nitronates, particularly silyl nitronates, are often superior to nitrile oxides in their 13DC with olefins in terms of their ease of generation from nitroalkanes, stability, and the observed selectivity during cycloaddition. Cycloaddition of alkyl or silyl nitronates with olefins generates N-alkoxy- or N-silyloxy-substituted isoxazolidines which then undergo spontaneous or acid catalyzed elimination of alcohol (or silanol) to produce isoxazolines (see Scheme 1, Sect. 2). 

There exist a number of d -synthons, which are stabilized by the delocalization of the electron pair into orbitals of hetero atoms, although the nucleophilic centre remains at the carbon atom. From nitroalkanes anions may be formed in aqueous solutions (e.g. CHjNOj pK, = 10.2). Nitromethane and -ethane anions are particularly useful in synthesis. The cyanide anion is also a classical d -synthon (HCN pK = 9.1). 

Nitroalkanes show a related relationship between kinetic acidity and thermodynamic acidity. Additional alkyl substituents on nitromethane retard the rate of proton removal although the equilibrium is more favorable for the more highly substituted derivatives. The alkyl groups have a strong stabilizing effect on the nitronate ion, but unfavorable steric effects are dominant at the transition state for proton removal. As a result, kinetic and thermodynamic acidity show opposite responses to alkyl substitution. 

This reaction can also be applied to tertiary nitroalkanes lacking any additional functional group. The reactions with nitro compounds lacking additional anion-stabilizing groups are carried out in DMSO solution ... 

Secondary nitroalkanes also give silylnitronates, however, in decreased yields (30 40%)24. Due to their lower stability compared to silylnitronates derived from primary nitroalkanes. they arc prepared as tm-butyldirnethylsilyl derivatives. 

Jorgensen et al. [84] studied how solvent effects could influence the course of Diels-Alder reactions catalyzed by copper(II)-bisoxazoline. They assumed that the use of polar solvents (generally nitroalkanes) improved the activity and selectivity of the cationic copper-Lewis acid used in the hetero Diels-Alder reaction of alkylglyoxylates with dienes (Scheme 31, reaction 1). The explanation, close to that given by Evans regarding the crucial role of the counterion, is a stabilization of the dissociated ion, leading to a more defined complex conformation. They also used this reaction for the synthesis of a precursor for highly valuable sesquiterpene lactones with an enantiomeric excess superior to 99%. 

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

Table 3.5 gives the most typical examples of acyclic nitronic esters, which have unusually high thermal stability. These data contradict the known data on fast thermal decomposition of alkyl nitronates derived from the simplest nitroalkanes (237) and relatively low thermal stability of nitronate (73a). On the basis of the available data, the following empirical mle can be derived an extension of the conjugation chain of the nitronate fragment increases stability of nitronates. 

Regardless of the coordination mode of the boron atom, boryl nitronates are rather smoothly subjected to alkaline hydrolysis to give, after acidification, the corresponding nitroalkanes (217, 230, 316). Depending on stability of the aci form, the yields of nitroalkanes obtained vary from moderate to high (Scheme... 

The Ter Meer reaction has not been widely exploited for the synthesis of m-dinitroaliphatic compounds. This is partly because the Kaplan-Shechter oxidative nitration (Section 1.7) is more convenient, but also because of some more serious limitations. The first is the inability to synthesize internal em-dinitroaliphatic compounds functionality which shows high chemical stability and is found in many cyclic and caged energetic materials. Secondly, the em-nitronitronate salts formed in the Ter Meer reactions often need to be isolated to improve the yield and purity of the product. Dry em-nitronitronate salts are hazardous to handle and those from nitroalkanes like 1,1,4,4-tetranitrobutane are primary explosives which can explode even when wet. Even so, it is common to use conditions that lead to the precipitation of gem-nitronitronate salts from solution, a process that both drives the reaction to completion and also provides isolation and purification of the product salt by simple filtration. Purification of em-nitronitronate salts by filtration from the reaction liquors, followed by washing with methanol or ethanol to remove occluded impurities, has been used, although these salts should never be allowed to completely dry. 

Bowman and co-workers synthesized 2-azido-2-nitropropane by treating the sodium salt of 2-nitropropane with a mixture of sodium azide and potassium ferricyanide. Olah and co-workers used the same methodology for the synthesis of alicyclic gem-azidonitroalkanes from secondary nitroalkanes. Isomeric azidonitronorbornanes (38) and (39) were synthesized from 2,5-dinitronorbornane (37). Some of the gem-azidonitroalkanes synthesized during this work have poor chemical and thermal stability. 

Cyclization of nitro-stabilized radicals provides another method for the generation of cyclic nitronates (221). Oxidation of the aci-foim of nitroalkanes with ceric ammonium nitrate generates the ot-carbon centered radical, which in the presence of an alkene, leads to the homologation of the a-radical. In the case of a tethered alkene of appropriate length, radical addition leads to a cyclic nitronate (Scheme 2.20). 

The results indicate that the kinetic acidity is markedly lower for phosphonium salts than for the corresponding nitroalkanes, but cannot be correlated with pKa values. In contrast, the measurement of kinetic acidity using double potential step chronoamperometry180 allowed the determination of pka values for a series of phosphonium salts corresponding to semi-stabilized or non-stabilized ylides ... 

Use of proline as a catalyst has become an important methodology in the catalytic asymmetric addition of stabilized carbanions to conjugated carbonyl compounds. Hannessian employed L-proline (S)-l in the addition of nitroalkanes to enones (Scheme 1) [5]. In the presence of 3-7 mol % of (S)-l and an excess of trans-2,5-dimethylpiperazine in chloroform, comparable or higher enantiose-lectivities were attained compared to the Yamaguchi s method using L-proline... 

This anomeric stabilization of radicals is also observed using halonitrosugars such as 1-C-nitroglycosyl halides [22] 15. Captodative stabilization of the alcoxy nitro radicals explains the radical-chain substitution with mild nucleophiles such as ma-lonate or nitroalkane anions to form 16 (Scheme 8). 

The 1,4-addition (or conjugate addition) of resonance-stabilized carbanions. The Michael Addition is thermodynamically controlled the reaction donors are active methylenes such as malonates and nitroalkanes, and the acceptors are activated olefins such as a,P-unsaturated carbonyl compounds. 

The third category of carbon acid substrates is nitroalkanes that readily dissociate to resonance-stabilized carbanions. The carbanions cannot be oxidized by loss of two electrons because of the instability of the resultant carbonium ion. Oxidation of nitroalkanes occurs through loss of nitrite ion. 

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