Catalytic Enantioselective Conjugate Addition Reaction Research Articles

ChemInform Abstract: Organocatalytic Enantioselective Conjugate Addition of 3‐Fluorooxindoles to Vinyl Sulfone.

AbstractHighly efficient catalytic enantioselective conjugate addition reactions of 3‐fluorooxindoles to activated vinyl sulfone (II) is achieved using a binaphthyl‐modified bifunctional urea catalyst bearing both central and axial chiral elements.

Catalytic asymmetric conjugate addition of α-fluoro β-ketophosphonates to nitroalkenes in the presence of nickel complexes

Abstract The catalytic enantioselective conjugate addition reaction of α-fluoro β-ketophosphonates to nitroalkenes promoted by chiral nickel complexes is described. Treatment of α-fluoro β-ketophosphonates with nitroalkenes under mild reaction conditions afforded the corresponding Michael adducts containing fluorinated quaternary stereogenic center with excellent enantioselectivity (up to >99% ee).

Organocatalytic Enantioselective Conjugate Addition of 3‐Fluorooxindoles to Vinyl Sulfone

Highly efficient catalytic enantioselective conjugate addition reactions of 3-fluorooxindoles to activated vinyl sulfone (II) is achieved using a binaphthyl-modified bifunctional urea catalyst bearing both central and axial chiral elements.

Organocatalytic Asymmetric Conjugate Addition of 3-Alkyl-Substituted Oxindoles to Vinyl Ketones

phosphate. 5 Although there have been reports for the catalytic enantioselective conjugate addition reaction of 3-aryl-substituted oxindoles to vinyl ketones, 5 a few examples for the catalytic enantioselective conjugate addition reaction of 3alkyl-substituted oxindoles to cyclic enones were reported using chiral primary or secondary amine catalysts. 6 Therefore, the development of alternative catalysts for the catalytic enantioselective conjugate addition reaction of 3-alkyl-substituted oxindoles to vinyl ketones would be highly desirable. As part of the research program toward the development of synthetic methods for the catalytic carbon-carbon bond formations, 7 we recently reported the organocatalytic conjugate addition reaction to α,β-unsaturated carbonyl compounds 8 and the other Michael acceptors. 9 In this communications, we wish to describe the enantioselective conjugate addition reaction of prochiral 3-alkyl-substituted oxindoles with vinyl ketones catalyzed by binaphthyl-modified bifunctional organocatalysts bearing both central and axial chiral elements. In an attempt to validate the feasibility of the organocatalytic enantioselective conjugate addition reaction of 3substituted oxindoles, we first investigated the reaction system with 3-benzyl oxindole 1a with methyl vinyl ketone (2a) in the presence of 10 mol % of catalyst in toluene at room temperature. We examined the impact of the structure of catalysts I-IV on enantioselectivities (Table 1, entries 1-4). Quinine-derived thiourea catalyst I was ineffective (Table 1, entriry 1). While binaphthyl-modified chiral bifunctional organocatalysts II-III bearing both central and axial chiral

Organocatalytic Enantioselective Michael Addition of α-Nitroacetate to α,β-Unsaturated Enones: A Route to Chiral γ-Nitro Ketones and δ-Keto Esters

The catalytic enantioselective conjugate addition reaction of α-nitroacetate to α,β-unsaturated enones promoted by chiral bifunctional organocatalysts is described. The treatment of α-nitroacetate to α,β-unsaturated enones afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are easily converted to chiral γ-nitro ketones and δ-keto esters.

P‐Stereogenic Pinene‐Derived Phosphoramidites and Their Use in Copper‐Catalyzed Conjugate Additions

AbstractNew P‐stereogenic phosphoramidites based on a (–)‐pinane framework were synthesized and investigated by NMR spectroscopic methods and single‐crystal X‐ray structural analysis. The reaction between cis‐pinandiol 2 and N,N‐dialkylphosphoramidous dichlorides, followed by protection with theBH3·THF adduct, afforded diastereomeric mixtures of PS and PR BH3–phosphoramidite complexes. After separation by column chromatography, these stereoisomers were obtained in a pure form. The BH3 group was further cleaved by treatment with Et2NH at elevated temperature and the obtained free phosphoramidite ligands were used for catalytic enantioselective conjugate addition reactions. As substrates, a series of cyclic and acyclic enones was employed and addition was carried out with Et2Zn in the presence of catalytic amounts of CuI thiophenecarboxylate (CuTC) and a phosphoramidite ligand. The results revealed that the configuration of the phosphorus center controls the configuration of the newly formed stereogenic center of the β‐alkylated ketones.

Enantioselective organocatalytic conjugate addition of α-nitroacetate to α,β-unsaturated ketones in water

Abstract The catalytic enantioselective conjugate addition reaction of α-nitroacetate to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of α-nitroacetate to α,β-unsaturated ketones under aqueous-phase reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are easily converted to chiral δ-keto nitroalkanes and δ-keto esters.

On the Role of DNA in DNA-based Catalytic Enantioselective Conjugate Addition Reactions

A kinetic study of DNA-based catalytic enantioselective Friedel-Crafts alkylation and Michael addition reactions showed that DNA affects the rate of these reactions significantly. Whereas in the presence of DNA, a large acceleration was found for the Friedel-Crafts alkylation and a modest acceleration in the Michael addition of dimethyl malonate, a deceleration was observed when using nitromethane as nucleophile. Also, the enantioselectivities proved to be dependent on the DNA sequence. In comparison with the previously reported Diels-Alder reaction, the results presented here suggest that DNA plays a similar role in both cycloaddition and conjugate addition reactions.

Enantioselective conjugate addition of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones catalyzed by chiral bifunctional organocatalysts

The catalytic enantioselective conjugate addition reaction of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones under mild reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are useful for the synthesis of chiral monofluoromethylated compounds.

Organocatalytic synthesis of quaternary stereocenter bearing a fluorine atom: enantioselective conjugate addition of α-fluoro-β-ketoesters to nitroalkenes

The catalytic enantioselective conjugate addition reaction of α-fluoro-β-ketoesters to nitroalkenes promoted by chiral bifunctional organocatalysts is described. The treatment of α-fluoro-β-ketoesters with nitroalkenes under mild reaction conditions afforded the corresponding Michael adducts containing a fluorinated quaternary stereogenic center with excellent enantioselectivity (up to >99% ee).

Catalytic asymmetric synthesis of the alkaloid (+)-myrtine

A new protocol for the asymmetric synthesis of trans-2,6-disubstituted-4-piperidones has been developed using a catalytic enantioselective conjugate addition reaction in combination with a diastereoselective lithiation-substitution sequence; an efficient synthesis of (+)-myrtine has been achieved via this route.