Double Michael Addition Research Articles

ChemInform Abstract: Catalytic Asymmetric Construction of Spirocyclopentaneoxindoles by a Combined Ru‐Catalyzed Cross‐Metathesis/Double Michael Addition Sequence.

AbstractThe ruthenium‐catalyzed cross‐metathesis of 3‐allyloxindoles (I) with ethyl acrylate followed by an asymmetric double‐Michael addition reaction of resulting oxindoles (III) with nitroolefins (IV) provides access to spirocyclopentaneoxindoles (V) with high diastereo‐ and enantioselectivity.

ChemInform Abstract: Synthesis of Novel Methylene Bridge Functionalized Bis(indolyl)methanes Thorough a Double Michael Addition.

AbstractThe simple synthesis of novel bis(indolyl)methylmalonates based on an acid‐catalyzed double Michael addition is described.

Investigation on the reactivity of isoxazol-5-ones towards 1,2-diaza-1,3-dienes: new entry to variously substituted (imidazol-2-yl)acetate and 1,3-oxazin-6-one derivatives

1,2-Diaza-1,3-dienes (DDs) undergo, under neutral conditions, N-nucleophilic attack from a 4-ethoxycarbonylisoxazol-5-one derivative. The first aza-Michael addition is followed by an intramolecular second, affording a fused heterobicyclic system that, upon ring opening and decarboxylation processes, gives rise to novel substituted imidazoles with an acetate functionality in the 2-position. On the contrary, under the same reaction conditions, 3-phenylisoxazol-5-one provides a double Michael addition at two units of DD involving first the C-4 and then the N-2 of the heterocycle. The resulting diadduct spontaneously undergoes ring-opening/ring-closing process that concludes with a ring enlargement of the heterocycle providing the 1,3-oxazin-6-one derivative.

Catalytic Asymmetric Construction of Spirocyclopentaneoxindoles by a Combined Ru-Catalyzed Cross-Metathesis/Double Michael Addition Sequence

Biologically important and synthetically challenging spirocyclopentaneoxindoles with four contiguous stereocenters including one spiroquaternary stereocenter have been constructed in good yields (72-87%) with excellent diastereoselectivity (16:1→30:1 dr) and enantioselectivity (93→99% ee) by a combined Ru-catalyzed cross-metathesis/organocatalyzed asymmetric double-Michael addition sequence.

Enantioselectivity in Organocatalytic Cascade Double Michael Addition Reaction: A Theoretical Study

We have investigated important intermediates and key transition states of the organocatalyzed cascade double Michael addition using density functional theory. The calculated results suggest that the reaction contains intermolecular nucleophilic addition and intramolecular cyclization, both involving the formation of two stereocenters. The iminium-enamine catalysis of secondary amine unit enables the cascade addition to proceed consecutively. As an electron transport, the iminium attracts the electron stream to promote the nucleophilic addition. Then enamine causes the electron stream to catalyze the cyclization. As H bond donor, the catalyst forms three types of C-H···O H bond with substrates. The enantioselectivity and diastereoselectivity are dominated by the catalyst backbone. Two group links of pyrrole-phenyl and pyrrole-silyl ether orient the reaction in paths with smaller rotations of the linked single bonds. Our conclusion is supported by NBO analysis and the predicted ee, dr values according to the experiment.

Chiral Counteranion Synergistic Organocatalysis under High Temperature: Efficient Construction of Optically Pure Spiro[cyclohexanone-oxindole] Backbone

The combination of a cinchona-based chiral primary amine and a BINOL-phosphoric acid has been demonstrated as a powerful and synergistic catalyst system for the double Michael addition of isatylidene malononitriles with α,β-unsaturated ketones, to provide the novel chiral spiro [cyclohexane-1,3'-indoline]-2',3-diones in high yields (88-99%) with excellent diastereo- and enantioselectivities (94:6-99:1 dr's, 95-99% ee's).

ChemInform Abstract: A Highly Organocatalytic Stereoselective Double Michael Reaction: Efficient Construction of Optically Enriched Spirocyclic Oxindoles.

AbstractA cinchona based organocatalyst is employed to enable the first asymmetric double Michael addition of 3‐substituted oxindoles and aryl substituted dienones (II).

ChemInform Abstract: Efficient Synthesis of Optically Active 4‐Nitro‐cyclohexanones via Bifunctional Thiourea‐Base Catalyzed Double‐Michael Addition of Nitromethane to Dienones.

Thiourea-modified cinchona alkaloids as bifunctional catalysts and a base could catalyze a stepwise [5+1] cyclization of divinyl ketones with nitromethane via double Michael additions, furnishing optically active 4-nitro-cyclohexanones with good yields, excellent diastereoselectivities (>20 ∶ 1) and high enantiomeric ratios (up to 97 ∶ 3).

Synthesis of novel fluorinated polymers: facile carbon–carbon bond formation aided by fluorine substituents

The footprints of a macromolecular synthetic chemist were left on the sands of time. Novel anionic addition polymerization of fluorinated vinyl monomers, which generally show poor homopolymerization reactivity, has been developed. Anionic polyaddition has been achieved by the double Michael addition of bis(2-trifluoromethylacrylate)s to active methylene compounds. Radical addition of fluorinated vinyl monomers with many organic compounds possessing carbon–hydrogen bonds has been accomplished and amplified to the polyaddition reaction to incorporate fluorinated vinyl monomers into polymer main chains. The facile carbon–carbon bond formation reactions have been accomplished by the aid of fluorine substituents.

Quinine‐Catalysed Double Michael Addition of Malononitrile to 1,5‐Disubstituted Pentadien‐3‐ones: A Stereoselective Route to Cyclohexanones

AbstractThe stereoselective synthesis of 4‐oxo‐2,6‐diaryl‐cyclohexane‐1,1‐dicarbonitriles has been developed through double Michael addition of malononitrile to 1,5‐disubstituted pentadien‐3‐ones catalysed by quinine. This simple cascade process affords cyclohexanones in moderate‐to‐good yields, excellent diastereoselectivity and up to 86 % ee. The isolation of the monoaddition product helps to shed light on thestereochemical outcome of the two‐step process.

ChemInform Abstract: Highly Diastereoselective Synthesis of Optically Pure Trifluoromethyl‐Substituted Imidazolidine, Oxazolidine and Thiazolidine.

AbstractA simple procedure is developed to allow the highly diastereoselective synthesis of the title compounds via a double Michael addition of chiral amides, amino alcohols or amino esters to the butanoate (I).

Efficient synthesis of optically active 4-nitro-cyclohexanones via bifunctional thiourea-base catalyzed double-Michael addition of nitromethane to dienones

Thiourea-modified cinchona alkaloids as bifunctional catalysts and a base could catalyze a stepwise [5+1] cyclization of divinyl ketones with nitromethane via double Michael additions, furnishing optically active 4-nitro-cyclohexanones with good yields, excellent diastereoselectivities (>20 : 1) and high enantiomeric ratios (up to 97 : 3).

Synthesis of Novel Methylene Bridge Functionalized Bis(indolyl)methanes through a Double Michael Addition

Synthesis of Novel Methylene Bridge Functionalized Bis(indolyl)methanes through a Double Michael Addition

ChemInform Abstract: Enantioselective Synthesis of Polysubstituted Cyclopentanones by Organocatalytic Double Michael Addition Reactions.

The O-TMS-protected diphenylprolinol-catalyzed cascade double Michael addition reactions of α,β-unsaturated aldehydes with a β-keto ester bearing a highly electron-deficient olefin unit occur smoothly to afford polysubstituted cyclopentanones. This process allows formation of four contiguous stereocenters in the cyclopentanone ring in one-step with excellent enantioselectivity.

Highly diastereoselective synthesis of optically pure trifluoromethyl-substituted imidazolidine, oxazolidine and thiazolidine

Optically pure trifluoromethylated imidazolidine, oxazolidine, and thiazolidine derivatives were synthesized through double Michael addition of chiral amino amides, amino acids, or amino alcohols to an easily available trifluoromethyl building block methyl (Z)-2-bromo-4,4,4-trifluoro-2-butenoate. These reactions occurred highly diastereo-selectively (up to 99:1) in good yields (65–96%) under mild conditions.

ChemInform Abstract: Efficient Construction of a 3C‐Xanthone‐Linked 3C‐Chromone Scaffold by Novel Double Michael Additions and Cyclizations.

AbstractThe reaction is promoted by DBU as a base and proceeds without any transition metal or inert atmosphere.

ChemInform Abstract: Diastereoselective Double Michael Additions of Vinylogous Esters and Thexyldimethylsilyl Triflate-Induced Cyclizations.

Abstract Double Michael additions of vinylogous esters of type 1 with crotyl ester generates diastereoselectively bicyclo[2.2.2]octanone 2 with four defined chiral centers via a synclinal transition state. Thexyldimethylsilyl enol ethers of type 5 and 10 undergo smooth cyclization to bicyclo[3.3.1]nonenones 7 and bicylo[3.3.0]octenones 12 by addition of Lewis acids.

ChemInform Abstract: Highly Stereoselective Double Michael Cyclization of 1-Phenylsulfinyl and Sulfonyl Analogues of the Nazarov Reagent.

The base-catalyzed double Michael addition of the β-keto sulfoxide 5 with 2-carbomethoxy-2-cyclohexenone (1) proceeds, after elimination of the sulfoxide moiety during chromatography on silica, to give the dehydrodecalin adduct 6 with high stereoselectivity.

Enantioselective Synthesis of Polysubstituted Cyclopentanones by Organocatalytic Double Michael Addition Reactions

The O-TMS-protected diphenylprolinol-catalyzed cascade double Michael addition reactions of alpha,beta-unsaturated aldehydes with a beta-keto ester bearing a highly electron-deficient olefin unit occur smoothly to afford polysubstituted cyclopentanones. This process allows formation of four contiguous stereocenters in the cyclopentanone ring in one-step with excellent enantioselectivity.

Efficient Construction of a 3C-Xanthone-Linked 3C-Chromone Scaffold by Novel Double Michael Additions and Cyclizations

A novel base-promoted cascade reaction of 2-methyl-3-(1-alkynyl)chromones to produce a 3C-xanthone-linked 3C-chromone scaffold has been developed. This tandem process involves multiple reactions such as Michael additions/cyclizations under mild conditions without a transition metal catalyst and inert atmosphere.