Additions nitroalkanes

P. Bako, A. Szolloy, P. Bombicz, L. Toke, Asymmetric C-C Bond Forming Reactions by Chiral Crown Catalysts Darzens Condensation and Nitroalkane Addition to the Double Bond , Synlett 1997, 291-292. 

Methi>ds of prcparaiion of nilroalkenes Recent reactions of formation of nilroalkenes C hemical properties of nitroalkanes Addition reactions Isomerization... 

There is also the issue of the possible role of nitroalkanes as intermediate products, especially that small amoimts of them were found in the oxidation at low temperatures. Specially designed experiments with Ci—C3 nitroalkanes RNO2 showed that their decomposition in the system without O2 gives low concentration of oxygenates, primarily aldehydes, with the product composition dominated by carbon oxides and alkenes (for C2—C3 nitroalkanes). Addition of O2 increases the yield of carbon oxides and simultaneously decreases the yield of oxygenates. In addition, for the C2—C3 nitroalkanes, the selectivity of formation of alkenes is always higher than that of oxygenates. 

Many of these reactions are reversible, and for the stronger nucleophiles they usually proceed the fastest. Typical examples are the addition of ammonia, amines, phosphines, and bisulfite. Alkaline conditions permit the addition of mercaptans, sulfides, ketones, nitroalkanes, and alcohols to acrylamide. Good examples of alcohol reactions are those involving polymeric alcohols such as poly(vinyl alcohol), cellulose, and starch. The alkaline conditions employed with these reactions result in partial hydrolysis of the amide, yielding mixed carbamojdethyl and carboxyethyl products. 

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 ... 

Tetraalkylairunonium fluorides or metal fluorides are also effective as catalysts for the Michael addition of nitroalkanes fsee. Table 4.2. ... 

Although the base-catalyzed addition of nitroalkanes to electron-deficient olefins has been extensively used in organic synthesis fsee Michael addition Chapter 4, it is only recently that the reaction has been extended to the cyclopropanadon reaction. In 1978, it was reported that the anion of nitromethane reacts with certain highly electron-deficient olefins to produce cycloptopanesingoodyieldrEq. 7.36. More recently, this reaction has been extended to more general cyclopropanadons, as shown in Eqs. 7.37 and 7.38, in which potassittm salts of nitroalkanes are employed in DMSO as alkylidene transfer reagents." ... 

The Michael addition of nih oalkanes to alkenes substituted with two elecbon-withdrawing groups at the a- and 3-positions provides a new method for the preparation of functionalized alkenes. Although reactions are not new, Ballini and coworkers have used this sbategy in the synthesis of polyfunctionalized unsaturated carbonyl derivatives by Michael addition of nih oalkanes to enediones as shown in Eqs. 7.124-7.126. Success of this type of reaction depends on the base and solvent. They have found that DBU in acetonihile is the method of choice for this puipose. This base-solvent system has been used widely in Michael additions of nitroalkanes to elechon-deficient alkenes (see Section 4.3, which discusses the Michael addition). ... 

AlkenyldQon using nitroalkanes foUowedby theselecQve reducQonof the double bends with NiCl and NdBbb, can be regarded as the addition of alkyl aruons to electron-deficient alkenes... 

To a stirred mixture of 0.2 mol of the nitroalkane, 7.8 mL of EtOH and 0.39 mL of 10 N aq sodium hydroxide is added 0.2 mol of the freshly distilled aldehyde, with the temperature being maintained at 30 35 C. After approximately two thirds of the aldehyde has been added, an additional 0.39 mL of 10 N aq sodium hydroxide and 1.5 mL of water are added, then the aldehyde addition is continued. The mixture is stirred at 38 C for 65 h and is then treated with ca. 4 mL of 2 N aq hydrochloric acid to pH 7. It is extracted with hexane and the combined extract is washed with three 50-mL portions of water and sat. aq NaCl, dried over MgSOj and evaporated to give the crude nitroaldol which is purified by bulb-to-bulb distillation. 

In the presence of a catalytic amount of tetrabutylammonium fluoride, either freshly dried over molecular sieves22 or as the trihydrate16, silylnitronates 2 derived from primary nitroalkanes react readily at — 78 C or below, via their in situ generated nitronates. with aromatic and aliphatic aldehydes to give the silyl-protected (/J, S )-nitroaldol adducts 3 in excellent yield4,22-24-26,27. Silylnitronates, derived from secondary nitroalkanes. afford the adducts in 30 40% overall yield24. In contrast to the classical Henry reaction (vide supra), the addition of silylnitronates to aldehydes is irreversible. Ketones are unreaetive under such conditions. 

A proof for the formation of alkyl radicals was found by their addition to the aci-nitromethane anion (CH2=N02 ) and by their reaction with p-benzoquinone to give the optically active nitroalkane radical-anion and the semiquinone radicals, respectively. In the case of di-r-butyl sulfoxide the f-butyl radical was observed directly by its absorption spectra. 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

As previously described, in basic conditions the proUne-derived a-sulfonyl amide 141 generates the imine function, which afterwards undergoes addition by a nucleophile, e.g., a nitronate ion see the diastereoselective synthesis of the diamino nitroalkane derivative 172, which is the precursor of the piperazine-2-carboxyUc acid 173, through a Nef reaction [45]. Similarly, the addition of the Uthium enolate of ethyl acetateto the a-sulfonyl amide 174 gave the diamino ester derivative 175, wich was then converted to (-)-l-aminopyrrolizidine 176 (Scheme 27). 

The aza-Henry reaction is the nucleophilic addition of nitroalkanes to imines to give nitroamine derivatives. This reaction was also studied with metal-based catalysts [164]. 

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. 

A significant acceleration of Michael addition was reported by Lubineau in the reaction of nitroalkanes with buten-2-one when the reaction media was changed from nonpolar organic solvents to water... 

Both overt carbanions and organometallic compounds, such as Grignard reagents, are powerful nucleophiles as we have seen in their addition reactions with C=0 (p. 221 et seq.) they tend therefore to promote an SN2 pathway in their displacement reactions. Particularly useful carbanions, in preparative terms, are those derived from CH2(C02Et)2, (3-ketoesters, l,3-( 3-)diketones, e.g. (55), a-cyanoesters, nitroalkanes, etc.—the so-called reactive methylenes ... 

---