Axially chiral guanidine as enantioselective base catalyst for 1,4-addition reaction of 1,3-dicarbonyl compounds with conjugated nitroalkenes

A new strategy for designing chiral guanidine molecules is presented, which features the introduction of an axially chiral binaphthyl backbone. The axially chiral guanidine catalysts thus developed facilitated the highly enantioselective 1,4-addition reaction of 1,3-dicarbonyl compounds with a broad range of conjugated nitroalkenes and showed extremely high catalytic activity.     

Direct generation of nucleophilic chiral palladium enolate from 1,3-dicarbonyl compounds: catalytic enantioselective Michael reaction with enones

Generation of chiral palladium enolates from 1,3-dicarbonyl compounds with the palladium aqua complex and its application to the highly efficient catalytic enantioselective Michael reaction with enones are described. The palladium aqua complexes are likely to supply Br?nsted base and Br?nsted acid successively during the reaction. The former activates the carbonyl compounds to give chiral palladium enolates, and the latter cooperatively activates enones. Using a catalytic amount (2-10 mol %) of the palladium complexes, the various 1,3-dicarbonyl compounds including diketones and beta-ketoesters were converted to the desired Michael adducts in good yields (69-92%) with excellent enantiomeric excesses (89-99% ee).     

Enantio- and diastereoselective Michael reaction of 1,3-dicarbonyl compounds to nitroolefins catalyzed by a bifunctional thiourea

We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we have developed a new synthetic route for (R)-(-)-baclofen and a chiral quaternary carbon center with high enantioselectivity by Michael reaction. In these reactions, we assumed that a thiourea moiety and an amino group of the catalyst activates a nitroolefin and a 1,3-dicarbonyl compound, respectively, to afford the Michael adduct with high enantio- and diastereoselectivity.     

Noyori’s Ts-DPEN ligand: an efficient bifunctional primary amine-based organocatalyst in enantio- and diastereoselective Michael addition of 1,3-dicarbonyl indane compounds to nitroolefins

Noyori’s Ts-DPEN ligand bearing an amino sulfonamide moiety and with a primary amino group on a chiral scaffold was found to be a simple and efficient bifunctional organocatalyst for the asymmetric Michael addition of 1,3-dicarbonyl compounds to nitroolefins, which gave highly functional Michael adduct with quaternary stereocenters in good enantioselectivities (up to 84%ee) and dr (up to 5.7:1 dr).     

Cu(OTf)2 catalyzed cross-coupling reaction of 1,3-dicarbonyl derivatives with 2-oxo-1-pyrrolidine compounds

An efficient method for the cross-coupling reactions of 1,3-dicarbonyl compounds with 2-oxo-1-pyrrolidine compounds 1 was developed. Cu(OTf)₂ catalyzed C–C bond forming reactions using substrates 1 with 1,3-dicarbonyl compounds in chloroform, providing the corresponding compounds of 2-oxo-1-pyrrolidine bearing 1,3-dicarbonyl moiety in moderate to good yields.     

Catalytic enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by well-defined chiral ru amido complexes

Well-defined chiral Ru amido complexes promoted asymmetric Michael addition of 1,3-dicarbonyl compounds including malonates, beta-keto esters, and 1,3-diketones to nitroalkenes to give the corresponding adducts with excellent ees and in excellent yields.     

Synthesis of chiral β -alkoxy- α,β -unsaturated ketones

The title compounds are synthesized in one-pot from the easily available sodium salts of unsymmetrical 1,3-dicarbonyl derivatives and chiral alkoxides.     

Biginelli reaction for synthesis of novel trifluoromethyl derivatives of bis(tetrahydropyrimidinone)benzenes

A facile one-pot three-component condensation of terephthalic aldehyde with urea and fluorinated 1,3-dicarbonyl derivatives is developed using catalytic quantities of chlorotrimethylsilane at ambient temperature. As a consequence, efficient synthesis of novel trifluoromethyl derivatives of bis(tetrahydropyrimidinone)benzenes is observed within short time periods. The procedure is shown to be equally efficient when urea is replaced with thiourea or guanidine.     

Gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with allylic alcohols

A highly efficient gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with allylic alcohols has been developed. The reaction was shown to proceed expediently for a wide variety of 1,3-dicarbonyl compounds and allylic alcohols, including 1° and terminal ones, under very mild conditions at room temperature in good to excellent yields (55-96%).     

Enantioselective Michael reaction of 1,3-dicarbonyl compounds to 3-nitro-2H-chromenes catalyzed by chiral nickel complexes

A chiral nickel complexes-catalyzed enantioselective Michael addition of 1,3-dicarbonyl compounds to 3-nitro-2H-chromenes has been developed; the products could be obtained in high yields and good enantioselectivities.     

An unusual Mannich type reaction of tertiary aromatic amines in aqueous micelles

An efficient, unusual Mannich type reaction of tertiary aromatic amines, formaldehyde and 1,3-dicarbonyl compounds is described in aqueous micelles catalyzed by boric acid to afford dialkylaminoarylated 1,3-dicarbonyls. In this unusual Mannich type reaction, tertiary aromatic amines react with formaldehyde to generate an N-alkyl-N-(4-methylenecyclohexa-2,5-dienylidene)alkylaminium intermediate (aza quinone methide), which undergoes nucleophilic addition with 1,3-dicarbonyl compounds. The reaction is highly regioselective, and exclusively para functionalized products are formed in high yields.     

Cerium Catalyzed Michael Addition of 1,3-Dicarbonyl Compounds Under Microwave Irradiation

Cerium chloride heptahydrate proves to be an efficient catalyst for Michael addition of 1,3-dicarbonyl compounds, through a simple solvent free reaction under microwave irradiations.     

Highly enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by designer chiral BINOL–quinine–squaramide: efficient access to optically active nitro-alkanes and their isoxazole derivatives

A chiral BINOL–quinine–squaramide has been identified as the best catalyst for the asymmetric Michael addition of nitroalkenes to 1,3-dicarbonyl compounds. A series of chiral nitroalkanes were prepared with approximately >99% ee. Furthermore, the methodology was applied successfully to the synthesis of enantiomerically pure isoxazoles derivatives (>99% ee).     

Organocatalytic enantioselective Michael addition of 2,4-pentandione to nitroalkenes promoted by bifunctional thioureas with central and axial chiral elements

Two novel bifunctional amine-thiourea organocatalysts 1 and 2, which both bear central and axial chiral elements, have been developed to promote enantioselective Michael reaction between 1,3-dicarbonyl compounds and nitro olefins. The catalyst 2 afforded the desired products with good levels of enantioselectivity (up to 96% ee), showing clearly that two chiral elements of 2 are matched, and enhance the stereochemical control.     

Formation of quaternary stereocenters by copper-catalyzed Michael reactions with L-valine amides as auxiliaries

Extensive investigations of chiral auxiliaries and active metals for Michael addition of 1,3-dicarbonyl compounds with vinyl ketones are summarized. Our efforts result in a widely applicable auxiliary-mediated, copper(II) acetate-catalyzed procedure. For these purposes, L-valine diethylamide is an optimal chiral auxiliary giving quaternary stereocenters with up to 99 % ee at ambient temperature. No inert or anhydrous conditions are required, the solvent is simply acetone, and the auxiliary can be recovered almost quantitatively after workup.     

Facile domino access to chiral mono-, bi-, and tricyclic 2,3-dihydrofurans

The asymmetric domino Michael-S(N)2 reaction of various 1,3-dicarbonyl compounds to α-bromonitroalkenes is described for the first time, employing readily available cinchona-derived bifunctional thioureas as organocatalysts. The novel transformations were highly regio-, chemo-, diastereo-, and enantioselective, which simultaneously gave the chiral tricyclic 2,3-dihydrofurans, bicyclic 2,3-dihydrofurans, and tetrasubstituted 2,3-dihydrofurans with two vicinal chiral carbon centers.     

Visible-light photoredox-mediated oxidation of N-methyl tertiaryamines under catalyst free conditions:Direct synthesis of methylene-bridged bis-1,3-dicarbonyl compounds

Mediated by visible light-induced photoredox catalysis and free of other catalysts, a new and efficient synthesis of methylene-bridged bis-l,3-dicarbonyl derivatives has been developed. A variety of N-methyl tertiaryamines and 1,3-dicarbonyl compounds were investigated in this reaction.     

Highly enantioselective direct Michael addition of 1,3-dicarbonyl compounds to β-fluoroalkyl-α-nitroalkenes

Cinchona alkaloid catalysts were used in the Michael addition reaction of 1,3-dicarbonyl compounds to β-fluoroalkyl-α-nitroalkenes for the first time. The catalytic system performed well over a broad scope of substrates including β-keto esters and 1,3-diketones with high diastereoselectivities and excellent enantioselectivities (up to 99% ee) under mild conditions. A wide range of useful fluorinated chiral building blocks was synthesized.     

Catalytic enantioselective construction of all-carbon quaternary stereocenters: synthetic and mechanistic studies of the C-acylation of silyl ketene acetals

With the aid of an appropriate chiral catalyst, acyclic silyl ketene acetals react with anhydrides to furnish 1,3-dicarbonyl compounds that bear all-carbon quaternary stereocenters in good ee and yield. Mechanistic studies provide strong support for a catalytic cycle that involves activation of both the electrophile (anhydride --> acylpyridinium) and the nucleophile (silyl ketene acetal --> enolate).     

A facile synthesis of indole-furan conjugates via integration of convergent and linear domino reactions

The convergent and linear domino reactions have been first integrated, for the first time, to provide an efficient synthesis of indole-furan conjugates from indoles, methyl ketones, and 1,3-dicarbonyl compounds.