Enantioselective Michael addition of aldehydes to nitroolefins catalyzed by pyrrolidine-HOBt

The oxytriazole catalyst “pyrrolidine-HOBt” developed for asymmetric Michael addition of cyclohexanone to nitroolefins is now evaluated for the asymmetric Michael addition of aldehydes to nitroolefins under similar reaction conditions. The results of this study indicate that, the oxytriazole catalyst “pyrrolidine-HOBt” is equally effective in promoting the Michael addition of aldehydes to nitroolefins on employing benzoic acid as an additive. The desired products, γ-nitrocarbonyl compounds were obtained in good yields and high enantioselectivities.     

Highly efficient asymmetric Michael addition of aldehydes to nitroalkenes with 4,5-methano-l-proline as organocatalysts

The 4,5-methano-l-prolines were used as chiral organocatalysts in asymmetric Michael addition of aldehydes to nitroolefins. These proline-like catalysts are unique for their rigid bicyclic structure with a cyclopropane and two H atoms attached to the bridgehead C atoms lying on the same side of the ring. They therefore showed high efficiency in asymmetric Michael addition of aldehydes to nitroolefins. Under the optimal conditions, excellent diastereo- and enantioselectivities (up to 97/3 dr and 98% ee) were obtained in high yields for a series of aldehydes and nitroolefins using only 5 mol % catalyst loading. The methodology features easily available catalysts, high catalytic efficiency and environmentally friendly procedures.     

Organic synthesis by means of noble metal compound—LI : Palladium-catalyzed addition of butadiene to nitroalkanes

Butadiene reacts with nitroalkanes in the presence of triphenylphosphine complexes of palladium, α-Hydrogens of nitroalkanes are displaced with 2,7-octadienyl groups to give nitroolefins. The nitroolefins thus obtained are reduced to give novel long chain amines, which have a primary amino group at the middle of the carbon chain.     

Highly efficient asymmetric Michael addition of aldehyde to nitroolefin using perhydroindolic acid as a chiral organocatalyst

Perhydroindolic acids, the by-products obtained in the industrial production of a trandolapril intermediate, were used as chiral organocatalysts in asymmetric Michael addition reactions of aldehydes to nitroolefins. These proline-like catalysts are unique for their rigid bicyclic structure with two H atoms attached to the bridgehead C atoms lying on the opposite side of the ring. They therefore showed high efficiency in asymmetric Michael additions of aldehydes to nitroolefins. Under the optimal conditions, excellent diastereo- and enantioselectivities (up to 99/1 dr and 98% ee) were obtained with high chemical yields for a series of aldehydes and nitroolefins using only 5 mol% catalyst loading. The methodology features easily available catalysts, high catalytic efficiency and environmentally green procedures.     

Adapting to substrate challenges: peptides as catalysts for conjugate addition reactions of aldehydes to α,β-disubstituted nitroolefins

Conjugate addition reactions of aldehydes to α,β-disubstituted nitroolefins are important because they provide synthetically useful γ-nitroaldehydes bearing three consecutive stereogenic centers. Such reactions are challenging due to the drastically lower reactivity of α,β-disubstituted nitroolefins compared to, for example, β-monosubstituted nitroolefins. The testing of a small collection of peptides of the type Pro-Pro-Xaa (Xaa=acidic amino acid) led to the identification of H-Pro-Pro-D-Gln-OH and H-Pro-Pro-Asn-OH as excellent stereoselective catalysts for this transformation. In the presence of 5 mol% of these peptides different combinations of aldehydes and α,β-disubstituted nitroolefins react readily with each other providing γ-nitroaldehydes in good yields and diastereoselectivities as well as excellent enantioselectivities. Chiral pyrrolidines as well as fully substituted γ-butyrolactams and γ-amino acids are easily accessible from the γ-nitroaldehydes. Mechanistic studies demonstrate that the configuration at all three stereogenic centers is induced by the peptidic catalysts. Only a minimal amount of products from homo-aldol reactions is observed demonstrating the high chemoselectivity of the peptidic catalysts.     

Synthesis of Polysubstituted Pyrrolizidines from Proline Derivatives and Conjugated Nitroolefins

The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and i-proline alkyl esters with several nitroolefins was investigated. Cyclic and acyclic nitroolefins add to the anti form of the ylide in a highly diastereoselective but poorly regioselective manner to give pyrrolizidine derivatives. In a few cases, the stereochemical results strongly support a stepwise mechanism.     

Action du monoxyde d'azote sur le phényléthylène et sur quelques arylalcènes

Nitric oxide reacts with phenylethylene and arylalkenes under the action of sunlight and at room temperature giving dimeric nitronitroso compounds prouved by IR. spectroscopy (see Table 2) and the corresponding nitroolefins. The main gaseous product is nitrogen as prouved by gaz liquid chromatography (see Table 1). The dimeric nitronitroso compounds can also be obtained by the reaction of dinitrogen trioxide with olefins. The structure of the nitronitroso compounds was further discussed. They may be reduced to give monoamines corresponding to the nitrogroup and may be also converted into nitroolefins.     

Green Procedure for the Synthesis of β-Nitro Sulfides by Michael Addition of Thiols to Nitroolefins

Michael addition of thiols to nitroolefins was carried out in water at room temperature without any catalyst, and β-nitro sulfides were obtained in excellent yields. This is the first example of Michael addition of thiols to nitroolefins in water without use of any catalyst. It provides a highly efficient, general, and practical green route to synthesis of β-nitro sulfides. Twenty-four new β-nitro sulfides were synthesized using this technique.     

Highly efficient and enantioselective Michael addition of acetylacetone to nitroolefins catalyzed by chiral bifunctional organocatalyst bearing multiple hydrogen-bonding donors

A new efficient catalyst system for the asymmetric addition of acetylacetone to nitroolefins using a chiral bifunctional organocatalyst bearing multiple hydrogen-bonding donors was developed. When using the organocatalyst 2c derived from natural cinchona alkaloid in optimal conditions, up to 98% chemical yield and 98% ee were observed with a variety of aromatic nitroolefins.     

Enantioselective conjugate addition of both aromatic ketones and acetone to nitroolefins catalyzed by chiral primary amines bearing multiple hydrogen-bonding donors

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90-96%) with high enantioselectivities (up to 97% ee).     

Catalytic asymmetric syntheses of isoxazoline-N-oxides under phase-transfer conditions

Catalytic asymmetric syntheses of various isoxazoline-N-oxides have been accomplished by asymmetric phase-transfer conjugate addition of bromomalonate to nitroolefins and subsequent ring-closing O-alkylation.     

Enantioselective copper(I) catalyzed 1,4-addition of diethylzinc to nitroolefins

The asymmetric 1,4-addition of diethylzinc to nitroolefins is efficiently catalyzed by copper(I) complexes with BINOL based phosphoramidite ligands.     

The synthesis of N-substituted β-(5-amino-2-furyl) nitroolefins

Studying nucleophilic substitution reactions in a number of β-(5-halo-2-furyl) nitroolefins (I) with secondary amines, we have shown for the first time the possibility of synthesizing the previously unknown N-substituted β-(5-aminofuryl)nitroolefins (II). We have found that the smoothest substitution reaction takes place in the case of the 5-halo-furylnitropropenes (I, R=CH₃) with morpholine and methylaniline when their alcoholic solutions are heated.     

Enantioselective organocatalytic conjugate addition of alpha-aminoketone to nitroolefins

The enantioselective organocatalytic conjugate addition of alpha-aminoketone to nitroolefins is reported.     

Synthesis of aza-Henry products and enamines in water by Michael addition of amines or thiols to activated unsaturated compounds

Nitroamines and nitrothiols were synthesized in high yields by the Michael addition of amines and thiols to nitroolefins without using any catalyst. Also, the reaction of amines with dimethylacetylene dicarboxylate (DMAD) in water afforded the corresponding enamines.     

Enantioselective organocatalytic Michael addition reactions between N-heterocycles and nitroolefins

[reaction: see text] A method for Michael addition of N-heterocycles to nitroolefins has been developed. The process is promoted by a cinchona alkaloid derivative to give Michael adducts in moderate to high enantioselectivities.     

Novel axially chiral bis-arylthiourea-based organocatalysts for asymmetric Friedel-Crafts type reactions

It has been shown that catalytic amounts (10-20 mol %) of novel axially chiral bis-arylthioureas promote the asymmetric organocatalytic Friedel-Crafts type addition of indole and N-methylindole to nitroolefins. The optimum catalyst is capable of promoting the reaction between challenging substrates such as N-methylindole and nitroolefins bearing aliphatic β-substituents with enantioselectivity unprecedented for an organocatalytic system.     

Reduction of α,β-unsaturated nitroolefins into nitroalkanes with Hantzsch ester promoted by isothiouronium salts

α,β-Unsaturated nitroolefins were reduced into nitroalkanes with a Hantzsch ester, promoted by S-benzyl isothiouronium iodide. The reactions proceeded successfully to afford the desired products in high yields and with excellent chemoselectivity.     

Asymmetric organocatalytic Michael-type reaction of phosphorus ylides to nitroolefins: synthesis of γ-nitro-β-aryl-α-methylene carboxylic esters

We report, for the first time, asymmetric organocatalytic Michael-type addition of stabilized phosphorus ylides to nitroolefins mediated by bisthiourea catalyst. Its subsequent reaction with formaldehyde provides γ-nitro-α-methylene carboxylic esters in moderate to good yields and enantioselectivities (up to 63% ee).     

A new synthesis of allylic alcohols or their derivatives via reductive elimination from γ-phenylthio-β-nitroalcohols with tributyltinhydride

Allylic alcohols are readily prepared by the Bu₃SnH-promoted elimination reaction from γ-phenylthio-β-nitroalcohls which are obtained by the joint reaction of nitroolefins, thiophenol, and aldehydes.