Nitroalkanes conjugated

Nitroalkane conjugate addition can be combined with other reactions... 

The stereospecific base-cleavage of the trimethylsilyl group in 1,3-dithiane 1-oxides 499 enables to obtain the specifically deuteriated products 500 (equation 303), A nitro group in y-nitroalkyl sulphoxides 501 (obtained by the Michael addition of nitroalkanes to a, j8-unsaturated sulphoxides) is replaced by hydrogen by means of tributyltin hydride (equation 304). This reagent does not affect the sulphinyl function. The overall procedure provides an efficient method for the conjugate addition of alkyl groups to a, -unsaturated sulphoxides . ... 

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. 

In recent years, there has been increased recognition that water is an attractive medium for organic reactions from the environmental point of view. The Michael addition of various nitroalkanes to conjugated enones can be performed in NaOH (0.025 M) and in the presence of cetyltrimethylammonium chloride (CTAC1) as cationic surfactant in the absence of organic solvents (Eq. 4.109).146 The Michael addition of nitromethane to methyl acrylate is carried out in water using NaOH as a base to give the mono adduct (Table 4.2).147... 

The Michael addition of nitroalkanes to a,P-unsaturated ketones followed by the Nef reaction has been extensively used as a method for the conjugated addition of acyl anions to enones (see Section 6.1, Nef Reaction). This strategy is one of the best methods for the preparation of 1,4-dicarbonyl compounds.156a h Various natural products have been prepared via this route.157 For example, r/.v-jasmone is prepared from readily available materials, as shown in Scheme 4.19.156f... 

Conjugate addition of nitroalkanes to ailyl Baylis-Hillman acetates in the presence of NaOH (0.6 N) in THF gives 2-alkylidene-4-nitro ketones with high stereoselectivity these are converted via the Nef reaction into the corresponding 1,4-diketones (Eq. 4.119).164... 

The sequence of the Michael addition of nitroalkanes and denitration provides a general method for conjugate addition of primary and secondary alkyl groups to electron deficient alkenes (Eq. 4.122).168... 

The synthesis of 2,3,5-trialkylpyrroles can be easily achieved by conjugate addition of nitroalkanes to 2-alken-l,4-dione (prepared by oxidative cleavage of 2,5-dialkylfuran) with DBU in acetonitrile, followed by chemoselective hydrogenation (10% Pd/C as catalyst) of the C-C- double bond of the enones obtained by elimination of HN02 from the Michael adduct. The Paal-Knorr reaction (Chapter 10) gives 2,3,5-trialkylpyrroles (Eq. 4.124).171... 

Yamaguchi and coworkers have found that proline rubidium salts catalyze the asymmetric Michael addition of nitroalkanes to prochiral acceptors. When (25)-L-prolines are used, acyclic ( )-enones give (S)-adducts. Cyclic (Z)-enones give (R)-adducts predominantly (Eq. 4.139).203 Recently, Hanessianhas reported that L-proline (3 7% mol equiv) and 2,5-dimethylpiperazine are more effective to induce catalytic asymmetric conjugate addition of nitroalkanes to cycloal-kanones.204... 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Silylation of Products of Conjugated Addition of Nucleophiles to a-Nitroolefins Nitroalkane anions can be generated not only by deprotonation of nitroalkanes (various modifications of these process were considered above) but also by the conjugated addition of nucleophiles 56 to a-nitroalkenes (42) (Scheme 3.56, Table 3.2). 

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. 

This process can be used with advantage for the preparation of conjugated nitroalkenes from nitroalkanes. It is of interest because the majority of known synthetic methods for generating nitroalkenes, the skeletons of target molecules, are generally assembled from simpler molecules (104). 

Conjugate addition of RN02 to enones. Primary nitroalkanes and a, (3-enones when activated by alumina form conjugate addition products that are oxidized in situ by alkaline hydrogen peroxide to 1,4-diketones. A similar reaction of nitromethane with a vinyl ketone provides 1,4,7-triketones. 

Reduction of nitroalkanes RNO2 with samarium(II) iodide, obtained from samarium and 1,2-diiodoethane, yields either alkylhydroxylamines RNHOH or alkylamines RNH2, depending on the amount of the reagent434. The base-catalysed reaction of nitroalkanes with phenyl(vinyl) sulphoxide (399) yields the conjugate adducts 400, which fragment to allylic nitro compounds 401 on thermolysis435. 

In a series of reports between 1991 and 1997 Yamaguchi showed that rubidium salts of L-proline (9) catalysed the conjugate addition of both nitroalkanes [29, 30] andmalonates [31-33] to prochiral a,p-unsaturated carbonyl compounds in up to 88% ee (Scheme 1). Rationalisation of the selectivities observed involved initial formation of an iminium ion between the secondary amine of the catalyst and the a,p-unsaturated carbonyl substrate. Subsequent deprotonation of the nucleophile by the carboxylate and selective delivery using ion pair... 

As previously noted (Scheme 1), prior to the explosion of interest in iminium ion catalysis as a platform for the activation of a,P-unsaturated carbonyl compounds in 2000, Yamaguchi [29-33] and Taguchi [34] showed that proline derived bi-func-tional catalysts could provide an effective platform for the ion-pair controlled conjugate addition of malonates and nitroalkanes to a, 3-unsaturated ketones with good levels of stereocontrol. 

The majority of recent contributions for the conjugate addition of C-H acids to a,p-unsaturated carbonyl compounds catalysed through iminium ion intermediates have come from the laboratories of Jprgensen. The ease with which 1,3-dicarbonyl compounds and nitroalkanes can be deprotonated, together with the soft nature of the nucleophile mean this is a particularly facile reaction which conveniently leads to useful precursors for further synthetic manipulation. 

Scheme 24 Conjugate addition of nitroalkanes to a,p-unsatutated ketones...

Fig. 5 Catalysts for the conjugate addition of nitroalkanes to acyclic Michael acceptors...

In a collection of insightful pieces of work Enders has incorporated an iminium ion conjugate addition of nitroalkanes to a,P-unsaturated aldehydes into a triple cascade reaction generating up to four contiguous stereocentres in one pot, again indicative of the complexity attainable from superficially simple catalysts and techniques [175-177] (Scheme 46). 

The conjugate addition of nitroalkanes to a,P-unsaturated aldehydes (Sect. 2.2.2) has been investigated by Uggerud, who compared the uncatalysed, proton catalysed and iminium ion catalysed additions [232]. The results suggested that protonated acrolein was more activated towards addition than the iminium ion catalysed process and also indicated that an intermediate oxazolidin structure 183, unobserved experimentally, may be involved in the reaction pathway (Fig. 17) with the transition state resembling that of a [3+2] cycloaddition process. 

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