Conjugate addition of nitroalkanes

Conjugate addition of nitroalkanes to ailyl Baylis-Hillman acetates in the presence of NaOH (0.6 N) in THF gives 2-alkylidene-4-nitro ketones with high stereoselectivity these are converted via the Nef reaction into the corresponding 1,4-diketones (Eq. 4.119).164... 

The synthesis of 2,3,5-trialkylpyrroles can be easily achieved by conjugate addition of nitroalkanes to 2-alken-l,4-dione (prepared by oxidative cleavage of 2,5-dialkylfuran) with DBU in acetonitrile, followed by chemoselective hydrogenation (10% Pd/C as catalyst) of the C-C- double bond of the enones obtained by elimination of HN02 from the Michael adduct. The Paal-Knorr reaction (Chapter 10) gives 2,3,5-trialkylpyrroles (Eq. 4.124).171... 

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... 

Scheme 24 Conjugate addition of nitroalkanes to a,p-unsatutated ketones...

Fig. 5 Catalysts for the conjugate addition of nitroalkanes to acyclic Michael acceptors...

In a collection of insightful pieces of work Enders has incorporated an iminium ion conjugate addition of nitroalkanes to a,P-unsaturated aldehydes into a triple cascade reaction generating up to four contiguous stereocentres in one pot, again indicative of the complexity attainable from superficially simple catalysts and techniques [175-177] (Scheme 46). 

The conjugate addition of nitroalkanes to a,P-unsaturated aldehydes (Sect. 2.2.2) has been investigated by Uggerud, who compared the uncatalysed, proton catalysed and iminium ion catalysed additions [232]. The results suggested that protonated acrolein was more activated towards addition than the iminium ion catalysed process and also indicated that an intermediate oxazolidin structure 183, unobserved experimentally, may be involved in the reaction pathway (Fig. 17) with the transition state resembling that of a [3+2] cycloaddition process. 

Conjugate addition of nitroalkanes to enones.5 This addition can be effected with basic alumina in the absence of a solvent at 25° in 50-88% yield. 

Maruoka and coworkers developed the diastereo- and enantioselective conjugate addition of nitroalkanes to alkylidenemalonates under mild phase-transfer conditions... 

As an extension of this research, Maruoka and coworkers succeeded in the catalytic asymmetric conjugate addition of nitroalkanes to cyclic a,[S-unsaturated ketones under phase-transfer conditions (Scheme 5.40) [39]. Here, the use of 3,5-bis(3,4,5-trifluorophenyl)phenyl-substituted catalyst (S,S)-lj is crucial for obtaining the high enantioselectivity. 

Pyrrolidin-2-yltetrazole has been found to be a versatile organocatalyst for the asymmetric conjugate addition of nitroalkanes to enones.45 Using this catalyst, this transformation requires short reaction times, tolerates a broad substrate scope, and possibly proceeds via generation of an iminium species. 

A highly diastereo- and enantio-selective formal conjugate addition of nitroalkanes to nitroalkenes has been achieved using a chiral ammonium bifluoride catalyst (9)46 This strategy provides a reliable route to optically active 1,3-dinitro compounds. 

The proline-catalyzed conjugate addition of nitroalkanes was further developed by Hanessian and Pham, resulting in enantiomeric excesses up to 93% in the addition of a variety of nitroalkanes to cyclic enones (Scheme 4.14) [27]. In their catalytic system, L-proline (3-7 mol%) was employed together with equimolar amounts (relative to the substrate enones) of trans-2,5-dimethylpiperazine. The latter addi-... 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

General Procedure for Conjugate Addition of Nitroalkanes to a,) -Unsaturated Enones [26a-c] (p. 109)... 

Halland N, Hazell RG, Jprgensen KA (2002) Organocatalytic asymmetric conjugate addition of nitroalkanes to alpha,beta-unsaturated enones using novel imidazoline catalysts. J Qrg Chem 67 8331-8338... 

Conjugate addition of nitroalkanes to a,6-unsaturated carbonyl compounds has been achieved using basic alumina, in the absence of a solvent.36 3-Nitropropanal has been prepared by conjugate addition of nitrite anion to acrolein reduction to 3-nitropropanol was effected with borane-dimethyl sulphide.36 -Nitro-acids and u-nitro-esters have been prepared by ring cleavage of 2-nitrocycloalkanones (Scheme 163).362... 

Synthesis of pyrrolidine derivatives and lactones based on conjugate addition of nitroalkanes to electron-poor alkenes 05CRV933. 

Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes Recent Results Ballini, R. Bosica, G. Fiorini, D. Palmieri, A. Petrini, M. Chem. Rev. 2005, 105, 933. 

Chiral quaternary ammonium salts are competent phase-transfer catalysts for the conjugate addition of nitroalkanes to a,p-unsaturated ketones. Pioneering work by Wynberg and Colonna groups about the enantioselective Michael addition of nitroalkanes to chalcones employing chiral phase-transfer catalysts derived from Cinchona... 

On the other hand, V-spiro Cj-symmetric chiral biaryl derivative 119 shows remarkable reactivity and selectivity in the conjugate addition of nitroalkanes to cyclic enones under mild solid-liquid PTC (Scheme 2.62) [174], This class of... 

Scheme 2.62 Conjugate addition of nitroalkanes catalyzed by A -spiro chiral ammonium...

Conjugate Addition of Nitroalkanes to ot,P-Unsaturated Carboxylic Acid Derivatives... 

Conjugate Addition of Nitroalkanes to Vinyl Sulfones, Nitroolefins, and Alkylidene Malonates... 

Bifunctional alkaloid-derived thiourea catalyst 79 promotes the conjugate addition of nitroalkanes to l,l-bis(benzenesulfonyl)ethylene in toluene to afford the corresponding enantiomerically enriched y-sulfonyl derivatives at-10°C [183]. Although... 

Scheme 2.67 Asymmetric conjugate addition of nitroalkanes to vinyl sulfones...

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