Nitroalkenes 1,3-dicarbonyl compounds

Recently, very effective asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes has been reported, as shown in Scheme 4.10. The reaction of ethyl acetoacetate with nitrostyrene is carried out in the presence of 5 mol% of the preformed complex of magnesium triflate and chiral bis(oxazoline) ligands and a small amount ofW-methylmorpholine (NMM) to give the adduct with selectivity of 91%. The selectivity depends on ligands. The effect of ligands is presented in Scheme 4.10.63... 

Dianions or trianions derived from 1,3-dicarbonyl compounds react with nitroalkenes at low temperature to give the adduct, which undergoes a nitro-aldol type cyclization (Eq. 4.50).640... 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

Michael addition of 1,3-dicarbonyl compounds to conjugated prochiral nitroalkenes catalysed by (acac)2Ni and (acac)2Co has been reported to give up to 30% ee when carried out in the presence of cinchonidine.100... 

The axially chiral guanidine catalyst (155) (0.4-5 mol%) has been developed to facilitate the highly enantioselective Michael addition of 1,3-dicarbonyl compounds (g to a broad range of conjugated nitroalkenes (<98% ee).211... 

A highly enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes has been reported that employs a newly developed Ni(II)-(bis)diamine-based catalyst (174). The reaction scope includes substituted and unsubstituted malonates, /3-keto esters, and nitroalkenes bearing aromatic and aliphatic residues.202... 

It is possible to make 4-acylimidazoles from 1,3-dicarbonyl compounds nitrated in their enolic forms (Scheme 3.2.4). The resultant nitroalkenes form Af-alkenylformamides when reduced, and subsequent cyclization with formamide in formic acid gives the products, albeit in only moderate yields [27]. 

The reaction involves the amine-catalyzed conversion of an aldehyde into a nitroalkene by reaction with nitromethane followed by a transition-metal-catalyzed Michael addition of p-dicarbonyl compounds in the same reaction vessel. Typically, amine catalysts and nickel complexes are incompatible due to their tendency to chelate and to render each other inactive. However, microencapsulation of poly(ethyleneimine) (PEI) forms catalyst 140, which can successfully be used in tandem with the nickel-based catalyst 141 (Figure 3.6). 

Terada, M., Ube, H. and Yaguchi, Y. (2006) Axially chiral guanidine as enantioselective base catalyst for 1,4-addition reaction of 1,3-dicarbonyl compounds with conjugated nitroalkenes. Journal of the American Chemical Society, 128, 1454-1455. 

Michael addition of 1,3-dicarbonyl compounds to nitroalkenes with subsequent cyclization and loss of HNO2 yields furans (Equation (33)). 4,5-Annulated furans are also available by this route <57CB1215, 59LA(626)71, 78JCS(P1)1144, 80JOC2945, 83IJC(B)914, 8381027). 

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... 

There is also a modified version of Takemoto s catalyst, which incorporates a benzimidazole heterocycle as the H-bonding donor site in place of the thiourea moiety." This catalyst 82 has been tested with success in several Michael-type reactions of 1,3-dicarbonyl compounds to nitroalkenes, in particular focused on the use of malonates as donors (Scheme 4.20), providing the corresponding adducts in excellent yields and enantioselectivities. p-Ketoesters have also been tested, although in this case the performance of the catalyst was found to be highly dependent on the structure of the p-ketoester employed. It has also to be pointed out that the reaction required the incorporation of a Bronsted acid cocatalyst such as TFA for achieving the best enantioselectivity, although the presence of this co-catalyst did not have any influence in the catalytic activity. 

Scheme 4.22 Enantioselective Michael addition of 1,3-dicarbonyl compounds or related derivatives to nitroalkenes catalyzed by 83d.

Scheme 4.23 Proposed stereochemical model for the 83b-d-catalyzed Michael reaction of 1,3-dicarbonyl compounds to nitroalkenes.

Kobayashi et al. developed catalytic asymmetric 1,4-additions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands 39, 166 and 168. They found that calcium pyBOX catalysts could effectively mediate catalytic asymmetric additions of 1,3-dicarbonyl compounds 4 to nitroalkenes 86, N-Boc-imines 138 or unsaturated amides 49 giving products 165,167 and 170, respectively. Neutral coordinative ligands worked well in these reactions, giving a noticeably faster rate of reaction... 

The organocatalyzed cascade reaction of 1,3-dicarbonyl compounds with Morita-Baylis-HiUman acetates of nitroalkenes give access to benzo ]chro-man-type derivatives in good-to-exceUent yields and with high diastereo- and... 

Among the most successful catal)rtic systems employed in enantioselective nickel-catalysed Michael additions of nucleophiles to nitroalkenes is that developed by Evans and Seidel in 2005, which allowed enantioselectivities of up to 95% ee to be achieved in the enantioselective conjugate additions of 1,3-dicarbonyl compounds to nitroalkenes (Scheme 2.3). Products resulting... 

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