Nitro compounds Michael addition

Michael condensations are catalyzed by alkaU alkoxides, tertiary amines, and quaternary bases and salts. Active methylene compounds and aUphatic nitro compounds add to form P-substituted propionates. These addition reactions are frequendy reversible at high temperatures. Exceptions are the tertiary nitro adducts which are converted to olefins at elevated temperatures (24). 

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 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). 

After reduction of the nitro function of the porphyrin, the porphyrinamine intermediate can be reacted with z./l-unsaturated carbonyl compounds to yield porphyrins with a fused pyridine ring, which is formed by Michael addition, imine formation and dehydrogenation. 

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... 

The only acyl anion (6) equivalents we have met which will carry out Michael additions are nitro compounds (p Tig3 and 213) but the scales arc weighted against such a Michael reaction as the most hindered atom must be attacked. 

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... 

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... 

Polyfunctionalized nitro compounds are prepared by the Michael addition using 2-alkenyl-substituted 2-siloxycyclopropanecarboxylates as Michael acceptors (Eq. 4.120).165... 

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... 

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. 

The starting aUylic nitro compound is obtained by nitration of 2-methylpropene with NOz. Subsequent Michael addition to methyl vinyl ketone followed by Pd-cataly zed ally lie alkylation affords terpenoids. 

Allylic nitro compounds undergo [2.3]sigmatropic rearrangement to afford rearranged alcohols, as shown in Eq. 7.4346 and Eq. 7.44 47 Because the allylic nitro compounds used in these reactions are readily prepared either by the Henry reaction or the Michael addition, these reactions may be useful in organic synthesis. 

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... 

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... 

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. 

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... 

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... 

Nitro compounds have been extensively used for synthesis of pyrrolidines as discussed in Chapter 4 on the Michael addition and Chapter 8 on cycloaddition. Tandem [2 + 4]/[2 + 3]... 

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