Catalytic enantioselective conjugate addition of indoles to simple α,β-unsaturated ketones

Chiral [Al(salen)Cl] complex (10 mol%) in the presence of 2,6-lutidine (10 mol%) was found to be effective in catalysing the enantioselective Friedel-Crafts-type conjugate addition of indoles (3) to (E)-arylcrotyl ketones (2), furnishing the corresponding β-indolyl ketones in excellent yield and high enantioselectivity (ee up to 89%).     

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

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.     

Gold(III)-catalyzed tandem conjugate addition/annulation of 4-hydroxycoumarins with α,β-unsaturated ketones

An efficient and selective approach for the synthesis of functionalized pyranocoumarins has been developed via a gold(III)-catalyzed tandem conjugate addition/annulation reaction of 4-hydroxycoumarins with α,β-unsaturated ketones.     

Cobalt-catalyzed conjugate addition of silylacetylenes to α,β-unsaturated ketones

Catalytic addition of silylacetylenes to α,β-unsaturated ketones proceeded in the presence of a cobalt complex coordinated with a bisphosphine ligand to give high yields of β-alkynylketones.     

Asymmetric conjugate addition of malonate to α,β-unsaturated ketones in water using a perfluoroalkanesulfonamide organocatalyst

Perfluoroalkanesulfonamide organocatalyst 7 efficiently promotes asymmetric Michael additions of malonates to enones in cyclohexane or water to produce the corresponding addition products with excellent yields and with up to 99% ee.     

Copper-catalyzed enantioselective 1,4-conjugate addition of dialkylzinc reagents to α,β- and α,β,γ,δ-unsaturated ketones

An enantioselective Cu(II)-catalyzed conjugate addition of dialkylzinc reagents to α,β- or α,β,γ,δ-unsaturated ketones with chiral cyclohexane-based amidophosphine ligands was developed. With 2 mol% of Cu(OAc)₂·H₂O/L5, the conjugate addition of diethylzinc to α,β-unsaturated ketones was achieved in good-to-excellent yields (up to 98%) and high enantioselectivities (up to 92% ee). This catalytic system was shown to be efficient for the 1,4-conjugate addition of Et₂Zn to (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one with 85% yield and 90% ee. Moreover, with 1 mol% of Cu(OTf)₂/L11, the conjugate addition of α,β,γ,δ-unsaturated ketones was accomplished with 1,4-regioselectivity, good yields (79–86%) and excellent enantioselectivities (up to 97% ee).     

Conjugate addition of unactivated thiols to α,β-unsaturated ketones catalyzed by a bifunctional rhenium(V)–oxo complex

ReOCl₃(OPPh₃)(S(CH₃)₂) has been found to be an efficient bifunctional catalyst for the 1,4-addition of thiols to α,β-unsaturated ketones. The addition of thiophenol derivatives and alkyl thiols proceeds under mild reaction conditions without pre-activation of the thiol or exogenous base. Reactions of aryl, alkyl, and cyclic enones produce the corresponding β-sulfanyl ketones in good to excellent yield.     

Conjugate addition to α,β-unsaturated ketones with mixed lithium triorganozincates

Lithium Triorganozincates of the type RR′₂ZnLi, where R′ = Me and R = n-Bu or sec-Bu, efficiently transfer the R group in a 1,4 fashion to α,β-unsaturated ketones.     

Highly enantioselective conjugate addition of 1-bromonitroalkanes to α,β-unsaturated ketones catalyzed by 9-amino-9-deoxyepiquinine

Asymmetric conjugate addition of 1-bromonitroalkanes to α,β-unsaturated ketones was studied using chiral primary amines as the catalysts. 9-Amino-9-deoxyepiquinine was found to be highly efficient catalyst for the transformation. 4-Bromo-4-nitroketones were obtained with excellent enantioselectivities (97-99% ee) and good yields (61-99%) for a variety of alkyl vinyl ketones. The product could be further debrominated with Bu₃SnH/AIBN to provide chiral 4-nitroketones in good yield and without loss of the optical purity.     

Recyclable graphite oxide catalyzed Friedel-Crafts addition of indoles to α,β-unsaturated ketones

The Friedel-Crafts addition of indoles to α,β-unsaturated ketones, and nitro styrenes was studied with graphite oxide as catalyst. Various indole derivatives were synthesized in good to excellent yields. The preparation of graphite oxide catalyst from simple and readily available starting materials makes this method more affordable. The heterogeneous graphite oxide can be easily recovered and recycled up to five cycles without loss of activity.     

Enantioselective sulfa-Michael addition of thioacids to α,β-unsaturated ketones with bifunctional organocatalyst

Organocatalytic conjugate addition of thioacids to α,β-unsaturated ketones has been studied in the presence of cinchona alkaloid derived urea catalyst. Both the enantiomers of products are accessible with the same level of enantioselectivity using pseudoenantiomeric quinine/quinidine derived catalysts. The catalytic process provides optically active thioesters with high chemical yields (up to 99%) and useful enantioselectivity (up to 83% ee). The reaction was performed with 1 mol % of catalyst in toluene at room temperature. A transition state model has been proposed to explain the stereochemical outcome of the reaction.     

Green, efficient and practical Michael addition of arylamines to α,β-unsaturated ketones

The aza-Michael addition of aromatic amines to α,β-unsaturated ketones was carried out effectively at room temperature in good to excellent yields without any catalyst or solvent. It was significant that part of adducts could be collected in almost quantitative yield without column chromatography. This procedure offered a green, efficient, and practical approach for the synthesis of β-amino ketones.     

Ethylene dinitrodiamine in the addition reaction to α, Β-unsaturated ketones

Summary The addition of ethylene dinitrodiamine to , -unsaturated ketones was investigated and it was established that the former is readily added to unsaturated ketones with formation of new N-nitroketones.     

Gallium trichloride-catalyzed conjugate addition of indole and pyrrole to α,β-unsaturated ketones in aqueous media

Michael addition of indole and pyrrole to a variety ofα,β-unsaturated ketones was efficiently promoted by a catalytic amount of GaCl_3 in aqueous media to afford the corresponding products in good to excellent yields.     

Trifluoroacetic anhydride—catalyzed conjugate addition of boronic acids to α,β-unsaturated ketones

The conjugate addition of boronic acids to α,β-unsaturated ketones catalyzed by acylating reagents has been explored. The results show that trifluoroacetic anhydride catalyzes the addition of vinylboronic acids under experimentally simple and metal-free conditions for a variety of substrates with good yields.     

Highly enantioselective Cu(I)-Tol-BINAP-catalyzed asymmetric conjugate addition of Grignard reagents to α,β-unsaturated esters

The copper-catalyzed conjugate addition (CA) of organometallic reagents to α,β-unsaturated carbonyl compounds is one of the most versatile synthetic methods for the construction of C-C bonds. Interestingly, the application of Grignard reagents, which are among the most widely used of organometallic compounds, in asymmetric conjugate addition (CA) reactions has received less attention. Therefore, our group and others have been exploring better catalytic systems to effect the asymmetric 1,4-conjugate addition of Grignard reagents to α,β-unsaturated esters. It is only in the past decade that significant breakthroughs have been made in this field. In our studies, we found that CuI-Tol-BINAP could catalyze the asymmetric conjugate addition (CA) reactions of Grignard reagents, including the addition of MeMgBr to α,β-unsaturated esters to afford the β-methylated esters in good yields with excellent regio- and enantioselectivities. Both enantiomers of the products could be obtained by either using the enantiomers of the chiral Tol-BINAP or by using the geometrical isomer of the starting material. This method is also suitable for other Michael acceptors. In this article, we describe the development of the asymmetric Cu(I)-Tol-BINAP catalyzed 1,4-conjugate addition of Grignard reagents to α,β-unsaturated esters and applications of this chemistry. This method provides a convenient method to synthesize β-alkyl esters with high enantioselectivity or diastereoselectivity using CuI and the inexpensive chiral ligand, Tol-BINAP.     

Ferrocenyl-substituted α,β-unsaturated ketones in synthesis of tetrahydropyrimidinones

Ferrocenyltetrahydropyrimidin-2-ones were prepared by reactions of linear and cyclic ,-unsaturated ketones of the ferrocene series with urea in i-PrOH in the presence of t-BuOK. The structures of the compounds prepared were studied by ¹H and ¹³C NMR and IR spectroscopy, and also by single crystal X-ray diffraction.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 11, 2004, pp. 1887–1893.Original Russian Text Copyright © 2004 by E. Klimova, Lorez, T. Klimova, Garcia, Hernandez, Ramirez.This revised version was published online in April 2005 with a corrected cover date.     

Organocatalytic enantioselective Michael addition reactions of fluoromalonates with α,β-unsaturated aldehydes

A new organocatalytic enantioselective Michael addition of α-fluoromalonate to enals has been developed.The process is efficiently catalyzed by readily available chiral diphenylpyrolinol TES ether under mild reaction conditions to afford versatile highly enantioenriched fluorinated aldehydes.