Nitroalkanes Michael reactions

Keywords cetyltrimethylammonium hydroxide, nitroalkane, Michael reaction, Henry reaction... 

The direct aziridinadon of nitroalkanes has been repotted for the first dme. Treatment of nitroalkene with an excess of CaO and NsONHCO-.Et fNs =4-nitroben2enesulfonyl gives the ct-nitroaziridine in good yields fEq. 10.70. ° The reaction proceeds via aza-Michael reaction followed by a ring closure. 

Michael reactions are base catalyzed and reversible, and so it is common to use either the nitronate salt of the nitroalkane substrate or the nitroalkane in the presence of a catalytic amount of alkali metal hydroxide, alkoxide or amine base. 

The Michael reaction of malonates to nitroolefins and the aza-Henry reaction of nitroalkanes to Al-phosphinoylimines are catalyzed by thiourea derivative 5a to provide the respective products in good and moderate enantioselectivities. Thiourea... 

Molecular iodine-promoted Michael addition is a simple and efficient method for generating 2-pyrrolyl-2-phenyl-l-nitroalkanes in good yields (Scheme 67) [86]. Cr+3-Catsan (Cr+3 exchanged commercially available montmorillonite clay) and ZnCl2, which were first used as Lewis acids for Michael reactions of pyrrole, showed different selectivity under the same conditions [221], In general, while the reactions catalyzed by Cr+3-Catsan... 

Further uses of nitroalkanes are in 1,4-additions (Michael reaction) to a,p-unsaturated carbonyl compounds and the like. Recent reports deal with transformations of 1,4-nitro ketones, 7, into 1,4-keto aldehydes, 8, and cyclization to cyclopentenones.16... 

NITROALKANES AS BUILDING BLOCKS FOR ONE-POT PROCESSES, VIA MICHAEL REACTION... 

One-Pot Process eor Both Nitroaldol (Henry) and Michael Reactions erom Primary Nitroalkanes... 

Ballini, R., Barboni, L., and Palmieri, A. 2007b. A new heterogeneous one-pot process for both nitroaldol (Henry) and Michael reactions from primary haloalkanes via nitroalkanes. Synlett, 19 3019-21. 

The Michael reaction of nitroalkanes with acrolein, catalyzed by tributylphosphine, followed by acet-alization of the resultant adduct, led to l,l-ethanediyldioxy-4-nitroalkane (202), which is oxidized by an electrolytic procedure to 4-oxoalkanal 1-acetal, the protected form of the expected 4-oxoalkanal (203 Scheme 47). 

As described in Sections 2.3.1.2 and 2.2.3, Choudary et al. recently revealed nanocrystalline magnesium oxide (NAP-MgO) as a recyclable heterogeneous catalyst [40, 45]. These authors extended the use of this new type of heterogeneous catalyst for the asymmetric Michael reaction of different acyclic enones with nitromethane and 2-nitropropane [69a]. In a Michael reaction of chalcone with nitromethane in THF solvent at -20°C, NAP-MgO/(lR,2R)-(-)-diaminocyclohexane (DAC) was found to be an excellent catalyst system (96% ee, 95% yield) (Scheme 2.32). This Michael reaction proceeds via the dual activation of both substrates (nucleophiles and electrophiles) by NAP-MgO. The Lewis basic site (O /O ) of the NAP-MgO activates the nitroalkanes, while the Lewis acid moiety (Mg /Mg )... 

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 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. 

A huge acceleration of the Michael reaction of nitroalkanes with methyl vinyl ketone was mentioned when going from non-polar organic solvents to water. The hydrophobic effect could be at least to some extent involved, since additives, such as glucose or saccharose, accelerate the reaction even more [72]. Cetyltrimethylam-monium chloride as an amphiphilic species which can influence the hydrophobic interactions was found to promote the Michael reaction of various nitroalkanes with conjugated enones in dilute aqueous solutions of sodium hydroxide [73],... 

Much work has also been devoted to Michael reaction of nitroalkanes to conjugated carbonyl compounds using 2A for catalysis. However, different additives (e.g., PhCOOH, ... 

Malonate and related activated methylene compounds have also been used as the nucleophile in conjugate addition/Michael reactions. Taylor and co-workers have developed a new methodology that utilizes (salen)aluminum complexes such as 43 as a catalyst to effect the enantioselective conjugate addition to a,p-unsaturated ketones by a variety of nucleophiles.25 For example, nitriles, nitroalkanes, hydrazoic acids, and azides have found utility in this reaction. Additionally, cyanoacetate (42) has been demonstrated to undergo a highly enantioselective conjugate addition to 41. The Krapcho decarboxylation is then necessary to produce cyanoketone 44, an intermediate in the synthesis of enantioenriched 2,4-cw-di substituted piperidine 45. 

Michael addition is one of the most efficient and effective routes to C-C bond formation[127]. This reaction is widely applied in organic synthesis and several new versions of it have been introduced recently. The commonly employed anionic alkyl synthons for Michael addition are those derived from nitroalkanes, ethyl cyanocarboxylates, and malonates, and their limitations have been largely overcome by newer methodologies. However, the newer approaches are by no means devoid of drawbacks such as long reaction times, modest product yields in many cases, and the requirement for excess nitroalkane. Michael addition reactions of Schiff s bases have long been known to constitute a convenient method for functionalizing a-amino esters at the a position and the ratio of Michael addition to cycloaddition product has been found to depend upon the metal ion employed to chelate the enolate produced upon deprotonation (see below). 

This reaction has general application in the synthesis of aldehydes and ketones, especially for 1,4-diketones and dihydrofurans. The 1,4-diketones can be prepared by the combination of a Michael reaction between a nitroalkane and an O, y0-unsaturated ketone followed by a Nef reaction, whereas dihydrofurans can be synthesized by the Nef reaction followed by cyclohydration. 

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