Michael addition of nitro compounds

The Michael addition of nitro compounds to electron-deficient alky nes affords aUyhc nitro compounds In good yields. In which KF-u-BmNClln DMSO Is used as a base and solvent fEq. 4.118. ... 

The Michael addition of nitro compounds to ct,fi-unsatiirated ketones or esters followed by reduction of the nitro to amino group is useful for the preparation of various heterocycles This is presented in Chapter 10 (Symhesis ofHatarocyclas). 

Intramolecular Michael addition of nitro compounds proceeds in a stereoselective way to give various types of cyclic nitro compounds with high stereoselectivity. The Michael addition of Tacetylcyclohexene to nitrostyrene followed by treatment with MeONa in MeOH gives 4-nitro-3-phenyldecalone with high stereoselectivity fEq. 4.128). 

Amide disconnection reveals (18) and FGl (amino to nitro) gives (19) which could be made by Michael addition of nitro compound (16) to an acrylate ester.. lalys-ts... 

In Table 4.1, the Michael addition of nitro compounds to various electron deficient alkenes is shown. 

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. 

Ballini and coworkers have used the Michael addition of nitro compounds followed by the Nef reaction for the synthesis of various spiroketalic pheromones (Scheme 4.21).159... 

Double Michael additions of nitro compounds bearing tethered acidic carbons to 3-butyn-2-one under NaH catalysis give nitrocyclohexanes with high stereoselectivity. The products are transformed into traws-fused bicyclic compounds via the Dickmann reaction on treatment with base. (Eq.4.129).176... 

The sequential process consisting of palladium-catalyzed alkylation and the intramolecular Michael addition of nitro compound provides a nitrocyclohaxane derivative, which is a good precursor for synthesis of Erythrina alkaloids (Eq. 4.131).179... 

Because reductive cleavage of aliphatic nitro compounds with Bu3SnH proceeds via alkyl radicals, nitro compounds are also used as precursors to alkyl radicals. Reactions using nitro compounds may have some advantages over other ones, since aliphatic nitro compounds are available from various sources. For example, the sequence of the Michael additions of nitro compounds provides an excellent method for the construction of quaternary carbon compounds (Eq. 7.79).126 Newkome has used this strategy for the construction of dendritic polymers (Eq. 7.80).127... 

X,P-Dehydro-a-amino acids are prepared by elimination of HN02 from P-nitro-a-amino acids, which are prepared by reaction of a-bromoglycine derivatives with alkyl nitronates (see Eq. 7.135).181 This process is a new type of the Michael addition of nitro compounds followed by elimination of HNOz. Such unusual amino acids are interesting as enzyme inhibitors.182... 

Michael addition of nitro compounds 246 to phenyl vinyl sulfoxides 247 in the presence of DBU in acetonitrile at room temperature gave adducts 248 in quantitative yields (82JOC5017). Other bases, such as triethylamine, potassium fluoride, and tetramethylguanidine, were not so effective as DBU. 

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Ni(II)(OAc)2bpy and Co(II)(OAc)2bpy catalyze the Michael addition of nitro-methane, malononitrile, and aniline to a,j8-unsaturated ketones, methyl acrylate, and acrylonitrile in DMF under neutral conditions [116]. FeCls 6H2O is a highly efficient catalyst of Michael reaction of 1,3-dicarbonyl compounds with a,/3-unsaturated ketones under mild and neutral conditions (Sch. 24) [117]. There is literature precedent for this reaction with dual catalysis Ni(II) immobilized on a clay support and FeCl3 to activate the enone [118]. The mechanism proposed for the single-center catalysis involves coordination of the enone to a diketonato complex [119]. The chemo-... 

The gross structures of the three compounds were confirmed as correctly represented by CVI, CVII, and CVIII by the unequivocal synthesis of ( )-pseudoheliotridane by Leonard and Felley (151, 152). The synthesis involved three steps (a) the Michael addition of nitro-methane to ethyl crotonate or diethyl ethylidenemalonate (CIX) ... 

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

The Michael addition of a nitrogen-centered nucleophile to nitroalkenes affords compounds that may serve as precursors of vicinal diamines, since the nitro group can be reduced to an amino function by reduction. The very convenient method for the preparation of 1,2-diamines is developed by the addition of C-ethylhydroxylamines to nitroalkenes followed by reduction with H2 in the presence of Pd/C (Eq. 4.24).30... 

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... 

Interesting intramolecular cyclization of 1-nitroalkyl radicals generated by one-electron oxidation of aci-nitro anions with CAN is reported. As shown in Eq. 5.44, stereoselective formation of 3,4-functionalized tetrahydrofurans is observed.62 l-Nitro-6-heptenyl radicals generated by one electron oxidation of aci-nitroanions with CAN afford 2,3,4-trisubstituted tetrahydropyrans.63 The requisite nitro compounds are prepared by the Michael addition of 3-buten-l-al to nitroalkenes. 

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. 

The hydrogenation in the presence of Pd/C is also effective for the conversion of nitro compounds to amines.94 The Michael addition of nitromethane to 2-alkenoic esters followed by catalytic hydrogenation using 10% Pd/C in acetic acid and hydrolysis is a convenient method for the preparation of 3-alkyl-4-aminobutanoic acids, which are important y-amino acids for biological study (Eq. 6.48).94b The reduction can be carried out at room temperature and atmospheric pressure. 

Sequential Michael additions are versatile methods for the construction of cyclic compounds. Although a variety of these reactions have been developed, the use of alcohols as nucleophiles for the Michael addition to nitroalkenes has been little studied. Recently, Ikeda and coworkers have reported an elegant synthesis of octahydrobenzo[b]furans via the sequential Michael addition of 1-nitro-cyclohexene with methyl 4-hydroxy-2-butynoate in the presence of t-BuOK followed by radical denitration (Eq. 7.74).94... 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

A one pot samarium-catalyzed three-component reaction of aldehydes, amines, and nitroal-kanes leads to pyrroles. The reaction proceeds via imines, generated from the amine and carbonyl compound, followed by the Michael addition of the nitro compound (Eq. 10.10).12a In... 

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

The base-catalysed Michael addition of a,/J-unsaturated nitro compounds 363 to electron-deficient olefins 364 (R4 = Ac, CC>2Me or CN) results in the formation of ally lie nitro compounds 365 aldehydes give alcohols 366 in this reaction409. 

Michael addition to unsaturated amides. This system (1 equiv. of each) effects Michael addition of ketones, nitro compounds, ethyl cyanoacetate, and diethyl malonate to a,(3-unsaturated amides. Addition to methacrylamides is interesting because the final products are glutarimides or dihydropyridinones. 

Stable epoxides of op -unsaturated carbonyl and nitro compounds have been obtained. For example, compound 24 reacts with hydrogen peroxide or alkyl hydroperoxides in the presence of a base to give 25.63 The reaction is believed to proceed by Michael addition of the hydroperoxide anion to 24, and subsequent intramolecular displacement of hydroxide by the anion of the carbon atom that bears the nitro group (Scheme 10). 

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