Enantioselective Michael addition of α,α-disubstituted aldehydes to maleimides organocatalyzed by chiral primary amine-guanidines

New primary amine-guanidines derived from the monoguanylation of (1S,2S)- and (1R,2R)-cyclohexane-1,2-diamine have been prepared and used as chiral organocatalysts for the enantioselective conjugate addition of α,α-disubstituted aldehydes to maleimides. The corresponding Michael adducts bearing a new stereocenter were generally obtained in high or quantitative yields and with good enantioselectivities (up to 93% ee).     

Solvent-dependent enantioswitching in the Michael addition of α,α-disubstituted aldehydes to maleimides organocatalyzed by mono-N-Boc-protected cyclohexa-1,2-diamines

Enantiomerically pure mono-N-Boc-protected trans-cyclohexa-1,2-diamines are used as organocatalysts for the enantioselective conjugate addition of α,α-disubstituted aldehydes to maleimides. Using a single enantiomer of the organocatalyst, both enantiomeric forms of the resulting Michael adducts bearing a new quaternary stereocenter are obtained in high yields, by only changing the reaction solvent from chloroform (up to 86% ee) to aqueous DMF (up to 84% ee).     

Enantioselective addition of organolithium reagents to quinoline catalyzed by 1,2-diamines

Some enantiomerically enriched 2-substituted-1,2-dihydroquinolines were obtained by the enantioselective addition of organolithium reagents to quinoline. 1,2-Diamines were used as external chiral ligands and enantiomeric excesses up to 64% were obtained.     

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.     

Chiral phosphoproline-catalyzed asymmetric Michael addition of ketones to nitroolefins: an experimental and theoretical study

A novel pyrrolidine-based chiral phosphoproline is an effective bifunctional organocatalyst for the asymmetric Michael addition of ketones to nitroolefins giving high levels of diastereo- and enantio-selectivities (up to > 99 : 1 dr and 96% ee). anti-SR Transition state has the lowest barrier which controls the stereoselectivity, in agreement with experimental results.     

Enantioselective Michael addition of isobutyraldehyde to nitroalkenes organocatalyzed by chiral primary amine-guanidines

Primary amine-guanidines derived from trans-cyclohexane-1,2-diamines are used as organocatalysts for the enantioselective conjugate addition of isobutyraldehyde to arylated and heteroarylated nitroalkenes. The reaction was performed in the presence of imidazole as the additive in aqueous DMF as the solvent at 0 °C. The corresponding Michael adducts bearing a new stereocenter were obtained in high yields and with enantioselectivities of up to 80%. Theoretical calculations are used to justify the observed sense of the stereoinduction.     

Direct enantioselective Michael addition of aldehydes to vinyl ketones catalyzed by chiral amines

Chiral amines such as (S)-2-[bis(3,5-dimethylphenyl)methyl]pyrrolidine and the C(2)-symmetric (2S,5S)-2,5-diphenylpyrrolidine can catalyze the direct enantioselective Michael addition of simple aldehydes to vinyl ketones. The conditions for this organocatalytic reaction have been optimized and it has been found that the chiral amines catalyze the formation of optically active substituted 5-keto aldehydes in good yields and enantioselectivities, using aldehydes and, e.g., methyl vinyl ketone as starting compounds. Taking into account that the chiral amine can activate the aldehyde and/or the enone, the mechanism for the reaction has been investigated. On the basis of intermediate synthesis, nonlinear effect, and theoretical investigations, the mechanism for the catalytic direct enantioselective Michael addition of aldehydes to vinyl ketones is discussed.     

Organocatalytic enantioselective conjugate addition of aldehydes to maleimides

The highly enantioselective direct organocatalytic conjugate addition of aldehydes to maleimides is presented.     

Enantioselective addition of diethylzinc to aryl aldehydes catalyzed by novel chiral imino alcohol ligands

The enantioselective alkylation of aryl aldehydes by diethylzinc in the presence of catalytic amounts of several novel chiral imino alcohol ligands, synthesized from the reaction of (R)-2-amino-1-butanol with aromatic aldehydes, was studied. The influence of temperature and ligand structure was investigated and enantioselectivity up to 81% was obtained.     

Enantioselective direct vinylogous Michael addition of functionalized furanones to nitroalkenes catalyzed by an axially chiral guanidine base

The highly syn-diastereo- and enantioselective direct vinylogous Michael addition of α-thio substituted furanones with conjugate nitroalkenes was demonstrated using an axially chiral guanidine base catalyst. The method provides facile access to enantioenriched α,γ-functionalized butenolides that can be further manipulated, thereby rendering them useful synthetic intermediates.     

Enantioselective Michael addition of malonates to aromatic nitroalkenes catalyzed by monosaccharide-based chiral crown ethers

The asymmetric Michael addition of diethyl malonate and α-substituted diethyl malonates to aromatic nitroalkenes was carried out under mild reaction conditions in a solid–liquid phase transfer reaction in the presence of α-d-glucopyranoside- and α-d-mannopyranoside-based crown ethers as the catalysts. The use of d-glucose-based lariat ether 1 gave the best results. The substituents of the β-nitrostyrene and the diethyl malonate had a significant impact on the chemical yields and enantioselectivity. The addition of diethyl-2-acetamidomalonate to aromatic nitroalkenes afforded the corresponding Michael adducts in moderate to high enantiomeric excess (ee up to 99%). The reaction of diethyl-2-methylmalonate with 2-nitro-β-nitrostyrene gave the adduct with 93% enantiomeric excess in the presence of crown catalyst 1.     

Enantioselective organocatalytic Michael addition of aldehydes to nitroethylene: efficient access to gamma2-amino acids

Enantioselective organocatalytic Michael addition of aldehydes to nitroethylene catalyzed by (S)-diphenylprolinol silyl ether provides beta-substituted-delta-nitroalcohols in nearly optically pure form (96-99% ee). The Michael adducts bear a single substituent adjacent to the carbonyl and can be efficiently converted to protected gamma2-amino acids, which are essential for the systematic conformational studies of gamma-peptide foldamers.     

Enantioselective addition of diethylzinc to aldehydes in the presence of chiral aprotic ligands

Optically active amino thiocyanate derivatives of (−)-norephedrine were found to act as effective aprotic ligands for enantioselective addition of diethylzinc to aldehydes. This reaction provided optically active secondary alcohols with ee up to 96%.     

Enantioselective rhodium-catalyzed addition of arylboronic acids to aldehydes using chiral spiro monophosphite ligands

[reaction: see text] Highly efficient rhodium-catalyzed asymmetric addition of arylboronic acids to aldehydes has been realized by using chiral spiro monophosphite ligands, affording diarylmethanols in excellent yields and good enantiomeric excesses.     

Catalytic enantioselective Michael addition of deconjugated butyrolactams to maleimides

The first catalytic enantioselective Michael addition of deconjugated butyrolactams to N-arylmaleimides is developed with the help of a bifunctional tertiary aminosquaramide catalyst. Unlike the widely explored and structurally related vinylogous nucleophile – deconjugated butenolides, deconjugated butyrolactams are found to be exclusively α-selective. The resulting highly substituted and densely functionalized products, bearing contiguous all-carbon quaternary and tertiary stereocenters, are formed in good yields with moderate diastereoselectivity and good to excellent enantioselectivity (up to 99:1 er).     

Enantioselective organocatalytic Michael addition of malonates to α,β-unsaturated aldehydes in water

The Michael addition of malonates to α,β-unsaturated aldehydes catalyzed by O-TMS protected diphenylprolinols and acetic acid in water occurs at 0 °C to rt. In most cases, the reaction runs to completion in less than 24 h. A wide range of aldehydes including β-aryl, β-alkyl and β-alkenyl acroleins are found to be compatible with these conditions, providing the corresponding adducts in good yields and with good to excellent enantioselectivities.     

Enantioselective synthesis of chiral 1,2-diamines by the catalytic ring opening of azabenzonorbornadienes: application in the preparation of new chiral ligands

In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl]₂ and (S,S′)-(R,R′)-C₂-ferriphos-tolyl, the asymmetric ring-opening reaction of N-Boc-azabenzonorbornadienes with dibenzylamine proceeded with excellent enantioselectivity (up to >99% ee) to give the corresponding 1,2-diamine scaffolds in high yields. The sequential deprotection of the ring-opened products and treatment with tartaric acid gave the enantiomerically pure 1,2-diamine tartrate salts. These salts were used for the preparation of new chiral ligands such as the salen-type ligands and Trost-type ligands.     

Enantioselective addition of diethylzinc to aldehydes induced by a new chiral Ti(IV) catalyst

A new chiral titanium reagent, derived from optically active trans-1,2-dicamphorsulfonamidocyclohexane 2a and Ti(OⁱPr)₄, was found to promote the enantioselective addition of diethylzinc to various aldehydes giving rise to the corresponding alcohols in high yields with moderate to high selectivity.     

Enantioselective addition of diethylzinc to aldehydes in the presence of chiral hydrazone and imine ligands

Optically active hydrazone and imine were found to act as effective ligands for enantioselective addition of diethylzinc to aldehydes. This reaction provided optically active secondary alcohols with ee up to 71%.     

Enantioselective addition of organometallics to aldehydes using camphor derived chiral 1,4-aminoalcohols as ligands

(+)-Camphor derived enantiomerically pure 1,4-aminoalcohols have been used as ligands in the addition reactions of n-BuLi and n-BuMgBr to benzaldehyde and in the reaction of diethylzinc with benzaldehyde and hexanal. All chiral secondary alcohols were obtained in good chemical yields and enantioselectivities were up to 87% ee in the addition of diethylzinc.