nitro-Michael Reaction Research Articles

Benzoimidazolyl Organoseleniums: Antioxidant Activity and Catalysts for Selective Iodination of Arenes and Nitro-Michael Reaction.

Here, the synthesis and catalytic activities of benzoimidazole-derived organoselenium compounds have been explored. The synthesized bis(2-benzoimidazolyl) diselenide, having increased Lewis acidity on the selenium center, outperforms simple phenyl and N-phenyl benzamide-based diselenides when compared for thiol peroxidase hydrogen peroxide decomposing antioxidant activity with a reduction rate of 18.6 ± 1.9 μM/s. The synthesized diselenide also acted as an efficient catalyst for the activation of N-iodo-succinimide toward the regioselective, monoiodination of electron-rich arenes and activation of nitro-alkene for nitro-Michael reactions for the first time.

A base-free copper-assisted synthesis of C2-symmetric spirotelluranes and biaryls based on divergent stoichiometry of Na2Te.

A one pot Cu(I)-assisted synthetic methodology has been developed for the preparation of biologically important C2-symmetric spirodiaza, benzyloxy and benzoxytelluranes from 2-bromo-N-aryl benzamides, benzyl alcohols, and benzoic acids by using the tellurium dianion (Te2-) under base-free conditions. Furthermore, C-C coupled biaryl 1,1'-diamides have been prepared by using an excess of Na2Te under the same reaction conditions. The synthesized spirodiazatelluranes served as a potent catalyst for the reduction of H2O2 and nitro-Michael reactions.

Chalcogen vs Halogen Bonding Catalysis in a Water-Bridge-Cocatalyzed Nitro-Michael Reaction.

Recently, a tellurium-based chalcogen-bond-catalyzed nitro-Michael reaction was reported ( Angew. Chem. Int. Ed. 2019, 58, 16923), taking advantage of the strong Lewis acidity of the catalyst. This species was found to be more effective than an analogous iodine-based halogen bond organocatalyst. Herein, we present a detailed mechanistic and kinetic analysis of these catalytic cycles including the influence of the solvent (and the performance of different intrinsic solvation models). While the chalcogen bonding interaction is fundamental to activate the C-C bond formation, we found that the presence of a two-water molecular bridge is critical to allow the following, otherwise high-energy proton transfer step. Even though the iodine-based halogen bonding interaction is stronger than the tellurium-based chalcogen bonding one, which makes the former a stronger Lewis acid and hence in principle a more efficient catalyst, solvation effects explain the smaller energy span of the latter.

Hierarchically assembled helicates as reaction platform - from stoichiometric Diels-Alder reactions to enamine catalysis.

The stereoselectivity of a Diels–Alder reaction within the periphery of hierarchically assembled titanium(IV) helicates formed from mixtures of achiral, reactive and chiral, unreactive ligands was investigated in detail. Following the pathway of the chiral induction, the chiral ligands, solvents as well as substituents at the dienophile were carefully varied. Based on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities.

Back Cover: Chalcogen Bonding Catalysis of a Nitro‐Michael Reaction (Angew. Chem. Int. Ed. 47/2019)

Chalcogen bonding is a noncovalent interaction between electrophilic chalcogen substituents and Lewis bases. In their Communication on page 16923 ff., S. M. Huber and co-workers show that dicationic tellurium compounds can act as strong catalysts in a nitro-Michael reaction. This is the first time that a nitro compound has been reported to be activated by halogen bonding or chalcogen bonding. The crucial role of chalcogen bonding was confirmed by comparison experiments.

NMR and Computational Studies on the Reactions of Enamines with Nitroalkenes That May Pass through Cyclobutanes.

The addition of aldehyde enamines to nitroalkenes affords cyclobutanes in all solvents, with all of the pyrrolidine and proline derivatives tested by us and with all of the substrates we have examined. Depending on the temperature, concentration of water, solvent polarity, and other factors, the opening and hydrolysis of such a four-membered ring may take place rapidly or last for several days, producing the final Michael-like adducts (4-nitrobutanals). Thirteen new cyclobutanes have now been characterized by NMR spectroscopy. As could be expected, s-trans-enamine conformers give rise to all-trans-(4S)-4-nitrocyclobutylpyrrolidines, while s-cis-enamine conformers afford all-trans-(4R)-4-nitrocyclobutylpyrrolidines. These four-membered rings can isomerize to adduct enamines, which should be hydrolyzed via their iminium ions. MP2 and M06-2X calculations predict that one iminium ion is more stable than the other iminium species, so that protonation of the adduct enamines can be quite stereoselective; in the presence of water, the so-called syn adducts (e.g., OCH–*CHR–*CHPh–CH2NO2, with R and Ph syn) eventually become the major products. Why one syn adduct is obtained with aldehydes, whereas cyclic ketones (the predicted ring-fused cyclobutanes of which isomerize to their enamines more easily) produce the other syn adduct, is also explained by means of molecular orbital calculations. Nitro-Michael reactions of aldehyde enamines that “stop” at the nitrocyclobutane stage and final enamine stage do not work catalytically, as known, but those of cyclic ketone enamines that do not work stop at the final enamine stage (if their hydrolysis to the corresponding nitroethylketones is less favorable than expected). These and other facts are accounted for, and the proposals of the groups led by Seebach and Hayashi, Blackmond, and Pihko and Papai are reconciled.

Chalcogen Bonding Catalysis of a Nitro-Michael Reaction.

Chalcogen bonding is the non‐covalent interaction between Lewis acidic chalcogen substituents and Lewis bases. Herein, we present the first application of dicationic tellurium‐based chalcogen bond donors in the nitro‐Michael reaction between trans‐β‐nitrostyrene and indoles. This also constitutes the first activation of nitro derivatives by chalcogen bonding (and halogen bonding). The catalysts showed rate accelerations of more than a factor of 300 compared to strongly Lewis acidic hydrogen bond donors. Several comparison experiments, titrations, and DFT calculations support a chalcogen‐bonding‐based mode of activation of β‐nitrostyrene.

Aminocatalytic Enantioselective 1, 6‐Addition of (Nitromethyl)benzenes to α, β, γ, δ‐Cyclic Dienones

An excellent regio‐, and enantioselective 1,6‐addition of (nitromethyl)benzenes to α, β, γ, δ‐cyclic dienones via nitro‐Michael reactions has been developed. With the application of cinchona‐based primary amine catalysts, various chiral ε‐nitro ketene compounds were obtained in moderate to high yields (up to 84 %) with high to excellent enantioselectivities (up to > 99 % ee).

Correction to " Anti-Selective Asymmetric Nitro-Michael Reaction of Furanones: Diastereocontrol by Catalyst".

Correction to " Anti-Selective Asymmetric Nitro-Michael Reaction of Furanones: Diastereocontrol by Catalyst".

Chiral Fullerene-Derived Thioureas as Recyclable Asymmetric Organocatalysts

Key words fullerenes - thioureas - Prato reaction - nitro-Michael reaction - recyclable catalysts

Enantioselective Approaches to 3,4-Annulated Indoles Using Organocatalytic Domino Reactions

Organocatalytic domino reactions of 4-substituted indoles are summarized in this account. Two reactions have been developed, one with enals, activated by secondary amine catalysts via iminium ions, and one with nitroethene, using a phosphoric acid catalyst. Both reactions required solving the challenge posed by the very low nucleo­philicity of the indole substrates, which bear an electron-withdrawing Michael acceptor at C4. DFT calculations were used to shed light on the unique reaction pathway followed by the phosphoric acid catalyzed transformation, wherein a bicoordinated nitronic acid intermediate was found to evolve preferentially through an intramolecular nitro-Michael reaction, instead of the common tautomerization pathway. These reactions provide new and efficient entries to 3,4-ring-fused indoles in dia­stereo- and enantioenriched form. In more detail, the structures obtained feature a 1,3,4,5-tetrahydrobenzo[cd]indole core, which is present in the structural framework of ergot alkaloids. Indeed, the preparation of an intermediate previously used in ergot alkaloid (6,7-secoagroclavine) synthesis was possible from one of the catalytic adducts.1 Introduction2 Reactions of 4-Substituted Indoles with α,β-Unsaturated Aldehydes Catalyzed by Secondary Amines3 Reactions of 4-Substituted Indoles with Nitroethene Catalyzed by Brønsted Acids4 Conclusion

Organocatalytic Asymmetric Nitro-Michael Reactions

The formation of C-C and C-X bonds is a fundamental process in synthesis. In recent years organocatalysis has become a powerful tool to achieve these steps in a highly stereoselective manner and the nitro-Michael reaction was frequently used. From the functionalization of simple aldehydes, ketones or dicarbonyl compounds to the synthesis of privileged heterocyclic structures often found present in naturally occurring bioactive compounds and pharmaceuticals, several developments are being continuously documented. This review is focused on the period Jan 2014-Mar 2015 and it highlights the novel prospects for targetoriented synthesis, including many novel domino and cascade processes initiated by nitro-Michael reactions. Keywords: Michael addition, Nitroalkene, Enantioselective, C-C bond formation, Domino, Nitroolefin.

Novel bifunctional l-prolinamide derivatives as highly efficient organocatalysts for asymmetric nitro-Michael reactions

A series of novel bifunctional l-prolinamide derivatives was synthesised, of which (S)-N-((S)-2-oxo-1-phenyl-2-(tritylamino)ethyl)pyrrolidine-2-carboxamide 6 was found to be the most effective catalyst in terms of both the yield and stereoselectivity for the nitro-Michael reaction of aldehydes to nitroalkenes. Under these optimized reaction conditions, 17 corresponding novel nitro-Michael addition adducts had high yields (up to 94%) and showed excellent diastereoselectivity (up to 99:1 dr) and enantioselectivity (up to 98 ee) under mild reaction conditions.

ChemInform Abstract: anti‐Selective Asymmetric Nitro‐Michael Reaction of Furanones: Diastereocontrol by Catalyst.

Catalyst-controlled switching of diastereoselectivity from high syn-selectivity (>98/2 dr, syn) to anti-selectivity (up to 96/4 dr, anti) of the asymmetric nitro-Michael reaction of furanones is described. Anti-diastereoselectivity of the nitro-Michael reaction is very rare. With 0.1–5 mol % loadings of an epi-quinine catalyst, the reaction of 5-substituted 2(3H)-furanones with nitroalkenes smoothly proceeded to give the anti-Michael adducts in good yields (up to 95%) with excellent diastereo- and enantioselectivities (up to 96/4 dr, anti; up to 99% ee). DFT calculations support a model that accounts the high anti-diastereoselectivity.

ChemInform Abstract: Bottom‐Up Synthesis of Supported Thioureas and Their Use in Enantioselective Solvent‐Free Aza‐Henry and Michael Additions.

Two sets of supported chiral thioureas, which differ in the length of the tether that connects the chiral appendage to the polymer structure and the effective functionalization, have been prepared by copolymerization of styrene, novel styryl thioureas derived from l-valine, and divinylbenzene. The efficiency of these polymeric thioureas has been tested in two different enantioselective transformations, namely, aza-Henry and nitro-Michael reactions, in neat reaction conditions. The obtained results show that it is possible to recycle the thiourea, and they are able to promote the reactions with good enantioselectivity at a low catalyst loading.

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

The catalytic activity of different supported bifunctional thioureas on sulfonylpolystyrene resins has been studied in the nitro-Michael addition of different nucleophiles to trans-β-nitrostyrene derivatives. The activity of the catalysts depends on the length of the tether linking the chiral thiourea to the polymer. The best results were obtained with the thiourea derived from (L)-valine and 1,6-hexanediamine. The catalysts can be used in only 2 mol % loading, and reused for at least four cycles in neat conditions. The ball milling promoted additions also worked very well.

Anti-Selective Asymmetric Nitro-Michael Reaction of Furanones: Diastereocontrol by Catalyst.

Catalyst-controlled switching of diastereoselectivity from high syn-selectivity (>98/2 dr, syn) to anti-selectivity (up to 96/4 dr, anti) of the asymmetric nitro-Michael reaction of furanones is described. Anti-diastereoselectivity of the nitro-Michael reaction is very rare. With 0.1-5 mol % loadings of an epi-quinine catalyst, the reaction of 5-substituted 2(3H)-furanones with nitroalkenes smoothly proceeded to give the anti-Michael adducts in good yields (up to 95%) with excellent diastereo- and enantioselectivities (up to 96/4 dr, anti; up to 99% ee). DFT calculations support a model that accounts the high anti-diastereoselectivity.

Bottom-Up Synthesis of Supported Thioureas and Their Use in Enantioselective Solvent-Free Aza-Henry and Michael Additions.

Two sets of supported chiral thioureas, which differ in the length of the tether that connects the chiral appendage to the polymer structure and the effective functionalization, have been prepared by copolymerization of styrene, novel styryl thioureas derived from l-valine, and divinylbenzene. The efficiency of these polymeric thioureas has been tested in two different enantioselective transformations, namely, aza-Henry and nitro-Michael reactions, in neat reaction conditions. The obtained results show that it is possible to recycle the thiourea, and they are able to promote the reactions with good enantioselectivity at a low catalyst loading.

Catalytic Activity of epi-Quinine-Derived 3,5-Bis(trifluoromethyl)benzamide in Asymmetric Nitro-Michael Reaction of Furanones.

High catalytic activity of novel epi-quinine-derived 3,5-bis(CF3)benzamide in the asymmetric nitro-Michael reaction is described. With 0.1-5 mol % loadings of this catalyst, the addition of 5-substituted 2(3-H)-furanones to a wide range of nitroalkenes involving challenging substrates, β-alkylnitroalkenes, smoothly proceeded, giving the Michael adducts in high yields (>90%) with excellent diastereo- and enantioselectivity (>98:2 dr, syn major; 88-98% ee). DFT calculation was carried out to account for the high catalytic activity.

A general, scalable, organocatalytic nitro-Michael addition to enones: enantioselective access to all-carbon quaternary stereocenters.

A tert-leucine-derived chiral diamine catalyzes the asymmetric Michael addition of nitromethane to five-, six-, and seven-membered β-substituted cyclic enones with excellent enantioselectivity, offering scalable, asymmetric access to all-carbon quaternary stereocenters. The reaction scope can be expanded to include linear acyclic enones, and excellent levels of enantioselectivity are also observed. Furthermore, this organocatalytic, asymmetric nitro-Michael reaction is amenable to multigram scale-up and applications in the construction of an eudesmane sesquiterpenoid skeleton.