Michael additions of nitroalkanes

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

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 . ... 

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... 

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... 

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 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. 

Nitroketones are reduced to pyrroles by diphenyl disulfide and triphenylphosphine (86JCS(Pl)2243). Since 7-nitroketones are accessible by Michael additions of nitroalkanes to enones, this is a potentially versatile method (Scheme 40). 

Chiral crown ether phosphine-palladium complexes have been used to catalyse the alkylation of carbanions derived from a-nitro ketones and a-nitro esters,63 and proline rubidium salts have been used to catalyse asymmetric Michael addition of nitroalkanes to prochiral acceptors 64 80% enantioselectivity can be achieved in each case. 

A rubidium salt of proline (5-10 mol%) has been reported to catalyse the asymmetric Michael addition of nitroalkanes to prochiral acceptors. When L-proline was used, acyclic (I )-enones produced (.S )-adducts. whereas cyclic (Z)-enones gave (R )-adducts.88... 

Michael additions. Michael addition of nitroalkanes to vinyl sulfoxides (equation 1) and to ketene diethyl dithioacetal S-monooxide (equation II) proceeds in high yield when DBU is used as base. The adducts can be converted into a,/J-enals.1... 

The Michael addition of nitroalkanes to a,f -unsaturated enones, catalysed by the novel chiral imidazolidine-2-yltetrazole (151), has been investigated. The new, more soluble organocatalyst decreases reaction times and improves enantioselectivities com- pared with other catalysts. The Michael addition adducts were obtained with up to 92% ee.179... 

Similar reactions could also be carried out with ketene diethyl dithioacetal S-monooxide (251). The Michael addition of nitroalkanes 246 to 251 afforded the selective monoadducts 252, but that to 247 (R = H) yielded a mixture of the mono- (248) and diadducts. 

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