Nitroalkenes as Michael acceptors

Different experimental and theoretical studies have been carried out in order to elucidate the exact reaction pathway which could account for the observed results and could also provide a reliable basis for the development of other 

Acetylacetone has also been the subject of several studies when used as 1,3-dicarbonyl compound suitable to engage in a Michael reaction with nitroalkenes under H-bonding catalysis. In this context, Takemoto s catalyst 68a and valine-derived thiourea 74 have been tested in the reaction with acetylacetone with nitrostyrene furnishing good results, although no extensive study was carried out in order to evaluate the substrate scope with regard to the substitution at the nitroalkene. On the other hand, several functionalized thioureas have been expressly surveyed in this reaction, providing a detailed study 

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

It also has to be remembered that enolizable aldehydes or ketones can also be used as Michael donors in this reaction using thiourea-containing catalysts for 

In this context, the reaction of 2-fluoromalonates with nitrostyrenes has also been successfully carried out using 83d as catalyst. The direct addition of nitroalkanes to nitroalkenes has also been performed using the same modified 

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Thiamine-catalyzed transformations are reversible, thus TV,/V-dialkyl hydrazones were selected as alternative acyl anion equivalents that were reported to react with electrophiles without acidic activation.41 One especially reactive example, formaldehyde hydrazone resin 13, was constructed from polymer-supported hydrazines and was employed in the first polymer-supported, uncatalyzed acyl anion additions (Fig. 8).38 As test substrates, nitroalkenes (as Michael acceptors) and activated aldehydes were selected. Reactivity of these acyl anion equivalents depended critically not only on the nature of the starting hydrazine, but also on the protocol for hydrazine formation. 

Racemic 3-alkyl oxindoles have also been found to be useful pro-nucleophiles in this context (Scheme 4.IS)." For this transformation, a modified version of Takemoto s catalyst was identified as the most efficient promoter of the reaction, which was found to have a remarkably wide substrate scope, allowing many different substitution patterns both at the oxindole and at the nitroalkene reagent, and even tolerating well the use of p-alkyl substituted nitroalkenes as Michael acceptors. Yields, diastereo- and enantioselectivities were found to be excellent in almost all the cases studied. The reaction also accepted very well the use of the simple nitroethene, another very challenging... 

For this reason, the only literature example regarding the use of nitroalkenes as Michael acceptors in enantioselective Michael reactions under PTC conditions is related to the use of oxindoles as pro-nucleophiles (Scheme 5.31). In this context, using deuterium labeling experiments, it was found that oxindoles underwent fast deprotonation in neutral aqueous media only in the... 

There is also an example of a one-pot reaction in which an initial Michael addition of a functionalized aldehyde containing an olefin moiety at the convenient position to a nitroalkene as Michael acceptor was followed by the formation of a 1,3-dipole and a subsequent intramolecular [3 + 2] cycloaddition (Scheme 7.12). In this case, ethyl 7-oxo-2-heptenoate was reacted with a series of nitroalkenes using 31a as catalyst and next A -hydroxylphenylamine was added to the reaction mixture, promoting the formation of the corresponding... 

Highly substituted cyclohexanes and cyclopentanes have been prepared by means of a cascade process involving the use of a nitroalkene as Michael acceptor and an a-substituted p-ketoester incorporating a lateral p-substituent with a terminal methyl ketone moiety at the convenient position, ready to... 

Du and coworkers have developed a stereoselective direct Michael addition of nitroalkanes to nitroalkenes catalyzed by quinine-derived dimeric squaramide 21 [93]. This transformation provided facile access to 1,3-dinitro compounds in high diastereo- and enantioselectivities starting from aryl-substituted nitroalkenes (Scheme 10.18). However, the use of an aliphatic nitroalkene as Michael acceptor resulted in a low yield and diminished enantioselectivity. While nitroethane and 1-nitropropane are excellent substrates, branched 2-nitropropane did not undergo the Michael addition reaction. The authors also noted that slightly reduced dias-... 

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