Nitroalkanes Michael addition

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). ... 

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 . ... 

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... 

The Michael addition of nitroalkanes to nitroalkenes is catalyzed by triethylamine to give 1,3-dinitro compounds (Eq. 4.45).60 In some cases, the intramolecular displacement of the nitro group takes place to give cyclic nitronates (Eq. 4.46).61... 

The Michael addition of nitroalkanes to election-deficient alkenes provides a powerful synthetic tool in which it is perceived that the nitro group can be transformed into various functionalities. Various kinds of bases have been used for this transformation in homogeneous solutions, or, alternatively, some heterogeneous catalysts have been employed. In general, bases used in the Henry reaction are also effective for these additions (Scheme 4.18).133... 

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 heterogeneous catalytic systems have some advantages over homogeneous reactions. Chemical transformations under heterogeneous conditions can occur with better efficiencies, higher purity of products, and easier work-up. Ballini and coworkers have found that commercial amberlyst A-27 is the best choice for the Michael addition of nitroalkanes with [ substituted alkene acceptors (Eq. 4.111).150 The reaction is also carried out by potassium carbonate in the presence of Aliquat 336 under ultrasonic irradiation (Eq. 4.112).151... 

The Michael addition of nitro compounds is a useful method for the preparation of various natural products. The Michael addition of nitroalkanes to dehydroalanines gives y-nitro-a-amino acids, which provides a convenient synthesis of side-chain modified a-amino acids (Eq. 4.114).152 Transformations of y-nitro-a-amino acid derivatives into a-amino acids occur by reductive denitration (see Section 7.2) into y-oxygenated a-amino acids by the Nef reaction (Eq. 

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... 

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... 

Ballini and coworkers have developed a new strategy for alkenylation of carbonyl compounds based on the Michael addition followed by elimination of HN02 (see Section 7.3). A variety of 2-alkylidene 1,4-dioles have been conveniently prepared, in two steps, by the Michael addition of a nitroalkane to the appropriate enedione derivatives under basic conditions, followed by chemoselective reduction with LiAlH4 (Eq. 4.123).170... 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200... 

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... 

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

The Nef reaction can also be carried out with reducing agents. Aqueous titanium chloride reduces nitro compounds to imines, which are readily hydrolyzed to carbonyl compounds (Eq. 6.17).28 The Michael addition of nitroalkanes to enones followed by reaction with TiCl3 provides an excellent route to 1,4-diketones and hence to cyclopentenones. For example, cw-jasmone is readily obtained,28 as shown in Eq. 6.18. 

Alumina-supported KF is an effective reagent for Michael addition of nitroalkanes to electron-deficient olefins. Subsequent cycloalkylations afford cyclopropanes.37 However, the reaction of a, 3-unsaturated ketones with nitroalkanes in the presence of KF-A1203 in acetonitrile gives 4,5-dihydrofuranes (Eq. 7.39).40... 

The Michael addition of nitroalkanes followed by denitration is also a useful method for the preparation of C-disaccharide. The Michael addition of glucosyl nitromethane to the levoglu-cosenone proceeds stereoselectively, and subsequent denitration gives the C-disaccharide in... 

Elegant application of the Michael addition of nitroalkanes to enones followed by denitration is demonstrated in the synthesis of (+) dihydromevinol, (see Scheme 7.9).75... 

Nitroethane undergoes base-catalyzed addition to C60 to give 2-hydroxy-1,2-dihydrofulleryl ketoxime by way of a unique intramolecular redox process, which is not observed in normal electron deficient alkenes (Eq. 8.77).128 (See Section 4.3 Michael addition of nitroalkanes). 

The Michael addition of nitroalkanes to a, P-unsaturated ketones gives y-nitroketones, which are converted into pyrroles by reduction of the nitro group with Bu3P and PhSSPh (Eq. 10.2).4... 

The C2-symmetric bifunctional tridentate bis(thiazoline) 222 has been shown to promote the zinc(II)-catalyzed asymmetric Michael addition of nitroalkanes to nitroalkenes in high enantioselectivity <06JA7418>. The corresponding bis(oxazoline) ligand provides comparable enantioselectivity but higher product yield. The same bis(thiazoline) ligand has also been evaluated in the enantioselective Friedel-Crafts alkylation of indoles, but the enantioselectivity is moderate <06OL2115>. 

The Michael addition of nitroalkanes to sugar-based a,p-unsaturated carbonyl compounds is another powerful method for the preparation of nitro sugar derivatives. 

Superoxide anion formed in situ in a solution exposed to air (i.e. with only a small concentration of O2) has been used as an EGB to generate nitroalkane anions that may add to activated alkenes or to carbonyl compounds [130, 131]. An example is shown in Scheme 33. The reaction is catalytic since the product anion can act as a base toward the nitroalkane. Using the nitroalkane as the solvent favors the proton transfer pathway over the competing addition of the product anion to a second molecule of activated alkene, a pathway that may lead to polymerization [130]. In some cases, better yields of the Michael addition product were obtained if a stoichiometric amount of the anion was formed ex situ (with O2 as the PB), and the activated alkene added subsequently ]130, 132]. 

The product of a Michael addition depends on the number of acidic protons present in the nitroalkane substrate. Nitroform, which has one acidic proton, can only react with one equivalent of Michael acceptor. Nitroform is a strong acid and sufficiently dissociated in solution so that it can be used in addition reactions without a base catalyst. The reaction of nitroform with unsaturated ketones has been investigated by Gilligan and Graff and used to synthesize a number of trinitromethyl-based explosives. 

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