Michael donors nitroalkanes

Michael condensations, together with the Diels-Alder cycloaddition and the aldol reactions, are the most powerful and useful bond-fonning reactions in synthetic organic chemistry. Like the nitro-aldol (Henry) additions, nitroalkanes are particularly appropriate reagents in Michael reactions they act as a-hydrogen donors. Nitroalkanes react easily with typical Michael acceptors such as a,p-unsaturated aldehydes or ketones under base or Lewis acid catalysis. ... 

In addition, it has been shown that the catalytic use of PS-N3PAPT (10 mol%) was very effective for Michael addition reactions of a variety of Michael donors such as p-ketoesters, ot-nitroketones and nitroalkanes with activated olefins such as methyl acrylate and methyl vinyl ketone [41] (Scheme 6.9). The recyclability of the catalyst was established after it had been used 12 times. When diethyl malonate or ethyl cyanoacetate was used as the Michael donor substrate, the expected disubstituted adducts were obtained in moderate to good yields. 

The use of nitroalkanes as Michael donors produces a particularly difficult situation mainly because of the chemoselectivity issues that have to be... 

In the same context, an intramolecular Michael reaction involving a nitroalkane as Michael donor and a simple a,p-unsaturated ester as Michael acceptor has been reported using hydroquinidine-derived thiourea 72a as... 

Cyclic ketones or acetone react with nitro-olefins, giving the corresponding -adducts hy action of the potassium salt of chiral p-chlorophenyl amino acid catalyst (18 examples, 40-99% anti syn 42 58-4 96 ee 61-95%). Malonates,2-nitroalkanes or p-ketoesters are useful Michael donors and can react with enones in the presence of lithium salts of primary amino acids to create a new carhon-carhon hond at the p-position of the ketone (Scheme 12.9). However in some cases p-amino acids were more efficient than the a-amino acids. ... 

TABLE 5.7. Asymmetric Michael Reaction between Nitroalkanes and Various Michael Donors Catalyzed by NAP-MgO at -20 °C Using (IR, 2R)-(—)-l,2-Diaminocyclohexane... 

Carbon-carbon bond forming reactions between carbanionic nucleophiles like enolates or deprotonated nitroalkanes and electron deficient alkenes and alkynes belong to the oldest and most versatile transformations known today (225-229). Moreover, stereoselective variants have proven to possess an enormous potential in the syntheses of complex molecules as already exemplified in Sect. 2.4. Whereas the applications depicted in this previous section utilized nucleophiles activated by enamine formation with a chiral secondary amine catalyst to achieve these highly selective C-C bond formations, the present discussirai will focus on the addition of carbon nucleophiles to iminium-activated Michael acceptors. Herein traditional Michael additions using e.g. enolate nucleophiles will be described whereas the use of aromatic Michael donors with iminium-activated acceptors in Friedel-Crafts type reactions will be discussed separately subsequently. 

Wang and co-workers [57,58] reported several Michael-type enantioselective additions with nitro-olefins. Under neat conditions, 1,3-dinitro compounds were generated in the 74 addition of nitroalkanes 75 to various P-substituted nitro-olefins (Scheme 15). Other Michael-type involving nitro-olefins reactions were illustrated using triazole donors 77 to offer good yields and high enantioselectivities (Scheme 16). 

The 1,4-addition (or conjugate addition) of resonance-stabilized carbanions. The Michael Addition is thermodynamically controlled the reaction donors are active methylenes such as malonates and nitroalkanes, and the acceptors are activated olefins such as a,P-unsaturated carbonyl compounds. 

Michael addition. Ostaszynski and Wielgat 58] used potassium (luoride as j talysi for the Michael addition of nitromethane to a double bond. (Alkali lorides were originally suggested by Yasuda ct al. [59] as catalysts foi the chael addition reactions.) The work of addition of nitroalkanes was continued J]- Various acceptors, for example, methylacrylate and acrylonitrile, were fd. Among nitroalkanes gem-dinitroalkancs were applied as donors. Nitro-ICS readily formed double salts with KHFj, RbHFj and CsHFj. The yield Ihe adducts of such salts with compounds containing a double bond varied reen 60 and 90%, viz. (5) ... 

In a typical work, the Michael reaction of several 1,3-dicarbonyl compounds, nitroalkanes and thiols as donors with various a,j3-unsaturated carbonyl acceptors on the surface of alumina in dry media have been described [23]. It was concluded that a dramatic improvement was obtained using this process when compared to the existing methods. The important features of this methodology are (a) no need for base, (b) no undesirable side reaction, (c) extremely fast addition, (d) mild reaction conditions, (e) easy set-up and work-up, (f) no toxic and expensive materials involved, and (g) high yields. 

The detailed mechanistic explanation pictures the initial weak interaction among the bifunctional thiourea catalyst 158, the malonic ester 157 as nucleophile, and the nitroalkane 140 as electrophile that should promote the first chemo- and stereoselective Michael addition. The resulting adduct A would be poised to participate directly in the second catalytic cycle by acting as donor in a regioselective ititro-Michael reaction with the a,p-unsaturated aldehyde 95, here activated as iminium ion by the secondary amine catalyst (5)-76. The new inteimediate B, with its aldehyde and malonate moiety suitably spatial disposed, would undergo a base-promoted aldol cychzation to efficiently generate the planned cyclohexanol 159 in moderate yield (up to 87%) and marvelous enantioselectivity (up to >99% ee). 

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