Michael-Henry Reaction Research Articles

Organocatalytic Activation of Unsymmetrical 2,3‐Diketones towards Catalytic Asymmetric Domino Michael–Henry Reaction

In this study, we explored a method to distinguish between both enolizable regions of unsymmetrical 2,3‐diketones in organocatalytic domino reactions involving nitroalkenes. The selective formation of an enamine from only one side of the molecule was made possible by the use of optically pure 2‐(trifluoromethyl)pyrrolidine. This catalyst, remarkably enhancing the reaction, owes its efficacy to a unique interplay between basicity and nucleophilicity. These features caused the enolization of the substrate at the second possible site to be omitted. The approach resulted in excellent regio‐ diastereo‐ and enantioselectivity (91‐99% ee) across various nitroalkenes, leading to the synthesis of novel cyclopentanone derivatives with three contiguous stereogenic center.

Diastereo- and Enantioselective Synthesis of Functionalized Cyclopentenes Containing a Quaternary Chiral Center via a Thiosquaramide-Catalyzed Cascade Michael-Henry Reaction.

An efficient method for the highly diastereoselective synthesis of chiral quaternary center-containing cyclopentenes via a cinchona alkaloid-derived thiosquaramide VIII-catalyzed tandem Michael-Henry reaction of phenacylmalononitriles and nitroolefins was deleveloped. Meanwhile, up to 98% of enantioselectivity was observed. A mechanism involving thiosqaramide-catalyzed asymmetric Michael addition and assisted E2 elimination was proposed based on experimental data and preliminary theoretical analysis (Hartree-Fock calculations).

Asymmetric Synthesis of Biaryl Atropisomers Using an Organocatalyst-Mediated Domino Reaction as the Key Step.

A three-pot synthetic method that features the use of an organocatalyst as the key step was developed for the preparation of biaryl atropisomers. The first reaction is an asymmetric domino Michael-Henry reaction catalyzed by diphenylprolinol silyl ether to afford the substituted nitrocyclohexanecarbaldehyde with four stereogenic centers and one defined configuration of a stereogenic axis with excellent enantioselectivity. Removal of the central chirality from the domino products afforded biaryl atropisomers having axial chirality with excellent enantioselectivity.

Novel Ammonium Ionic Liquid Supported (ILS) Diamine-Ni(II) Complexes Catalyzed Asymmetric Michael-Henry Cascade Reaction of 1,2-Dione with Nitroolefins

Novel Ammonium Ionic Liquid Supported (ILS) Diamine-Ni(II) Complexes Catalyzed Asymmetric Michael-Henry Cascade Reaction of 1,2-Dione with Nitroolefins

Catalyst-Controlled Switch in Diastereoselectivities: Enantioselective Construction of Functionalized 3,4-Dihydro-2H-thiopyrano[2,3-b]quinolines with Three Contiguous Stereocenters.

A tandem Michael-Henry reaction of 2-mercaptoquinoline-3-carbaldehydes with nitroolefins using hydrogen-bonding-based cooperative organocatalysts for the highly diastereodivergent synthesis of chiral functionalized 3,4-dihydro-2H-thiopyrano[2,3-b]quinolines with three contiguous tertiary stereocenters has been developed.

ChemInform Abstract: Access to Densely Functionalized Naphthalenes by Organobase Catalyzed Domino Reaction of 2‐(2‐Formylaryl)acetophenones with Nitroolefins.

AbstractAn one‐pot DABCO‐catalyzed domino Michael—Henry reaction of 2‐(2‐formylaryl)acetophenones with nitrostyrenes is developed to afford tri‐ and penta‐substituted naphthalenes.

Fiber-Supported Acid–Base Bifunctional Catalysts for Efficient Nucleophilic Addition in Water

A series of fiber supported acid–base bifunctional catalysts (FABCs) were developed by successive grafting of acrylic acid and 4-vinylpyridine onto the polypropylene fiber (PPF). The FABCs can efficiently catalyze a number of reactions whose key steps involve in nucleophilic addition. The obviously enhanced activities of the bifunctional catalysts compared with that of the individual fiber supported acid or base upon the nitro-aldol and Knoevenagel reactions indicate that the FABCs perform in a cooperative catalyzing model and their activities can be easily tuned by controlling the acid–base ratio. An optimized bifunctional catalyst was successfully applied to the aqueous Gewald, tandem Michael–Henry reaction and one three-component reaction with excellent catalytic performances. In addition, this newly developed bifunctional fiber catalyst also exhibits excellent recyclability and reusability with simple treatment.

ChemInform Abstract: Organocatalytic Enantioselective Michael—Michael—Henry Reaction Cascade. An Entry to Highly Functionalized Hajos—Parrish‐Type Ketones with Five to Six Contiguous Stereogenic Centers and Two Quaternary Carbons.

AbstractThe multicomponent reaction of 2‐methylcyclopentane‐1,3‐dione, nitroalkene, and α,β‐unsaturated aldehydes with the diphenylprolinol catalyst gives highly functionalized Hajos—Parrish‐type ketones with five to six contiguous stereocenters and two quaternary carbon stereogenic centers with high diastereoselectivity and enantioselectivity.

ChemInform Abstract: Asymmetric Domino Michael—Henry Reaction of 1,2‐Diones with Nitroolefins Catalyzed by a Chiral Bisoxazolidine—Ni(acac)2 Complex.

Abstract The asymmetric domino Michael–Henry reaction of 1,2-cyclohexadione with nitroolefins catalyzed by chiral ligand bisoxazolidine 1 and Ni(acac)2 has been developed. This process provided highly functionalized chiral bicycle[3,2,1] octane derivatives with the generation of four new stereogenic centers in high yields (76–99%), and with excellent enantioselectivities (up to 99%) and good diastereoselectivities (up to 9:1) under mild reaction conditions. The procedure presented is simple and makes this method suitable for practical use.

Asymmetric domino Michael–Henry reaction of 1,2-diones with nitroolefins catalyzed by a chiral bisoxazolidine–Ni(acac)2 complex

The asymmetric domino Michael–Henry reaction of 1,2-cyclohexadione with nitroolefins catalyzed by chiral ligand bisoxazolidine 1 and Ni(acac)2 has been developed. This process provided highly functionalized chiral bicycle[3,2,1] octane derivatives with the generation of four new stereogenic centers in high yields (76–99%), and with excellent enantioselectivities (up to 99%) and good diastereoselectivities (up to 9:1) under mild reaction conditions. The procedure presented is simple and makes this method suitable for practical use.

Nickel-Catalyzed Asymmetric Michael–Henry Reaction

Nickel-Catalyzed Asymmetric Michael–Henry Reaction

ChemInform Abstract: Synthesis of Optically Active 2H‐Thiopyrano[2,3‐b]quinolines with Three Contiguous Stereocenters via an Organocatalytic Asymmetric Tandem Michael—Henry Reaction.

Optically active 2H-thiopyrano[2,3-b]quinolines with three contiguous stereocenters have been synthesized via a chiral bifunctional squaramide-catalyzed tandem Michael–Henry reaction between 2-mercaptoquinoline-3-carbaldehydes and nitroolefins. The reactions proceed with excellent diastereo- and enantioselectivity to give the title compounds in high yields with high levels of diastereo- and enantioselectivity (up to >99/1 dr and >99% ee, respectively).

Synthesis of Optically Active 2H‐Thiopyrano[2,3‐b]quinolines with Three Contiguous Stereocenters via an Organocatalytic Asymmetric Tandem Michael–Henry Reaction

AbstractOptically active 2H‐thiopyrano[2,3‐b]quinolines with three contiguous stereocenters have been synthesized via a chiral bifunctional squaramide‐catalyzed tandem Michael–Henry reaction between 2‐mercaptoquinoline‐3‐carbaldehydes and nitroolefins. The reactions proceed with excellent diastereo‐ and enantioselectivity to give the title compounds in high yields with high levels of diastereo‐ and enantioselectivity (up to >99/1 dr and >99% ee, respectively).

Organocatalytic asymmetric domino Michael–Henry reaction for the synthesis of substituted bicyclo[3.2.1]octan-2-ones

The first organocatalytic asymmetric reaction between 1,4-cyclohexanedione and nitroalkenes has been studied, affording bicyclo[3.2.1]octane derivatives containing four continuous stereogenic centres. The products were obtained through a domino Michael-Henry process as a single diastereoisomer with excellent enantioselectivities.

Stereoselective synthesis of highly functionalized tetrahydrocarbazoles through a domino Michael–Henry reaction: an easy access to four contiguous chiral centers

For the first time, a very simple, efficient, mild, catalytic and one-step procedure for the synthesis of a series of densely functionalized 1-methoxycarbonyl-2-aryl-3-nitro-4-hydroxy-1,2,3,4-tetrahydro-9H-carbazole derivatives has been achieved via a domino Michael–Henry reaction of methyl 3-formyl-1H-indole-2-acetates with β-nitrostyrenes using DABCO as an organocatalyst. Furthermore, the high enantio-(≤92% ee) and diastereoselective (≤12 : 1 dr) synthesis of the title compounds has been achieved with excellent yields using 9-O-benzylcupreidine (10 mol%) as a catalyst.

Bifunctional Tertiary Phosphine-Catalyzed Cascade Michael–Henry Reaction of a β-Nitroolefin and a 2-(1-Substituted 3-oxo-3-phenylpropyl)malononitrile

The bifunctional phosphine catalyst 2′-(diphenylphosphino)biphenyl-2-ol was used in an effective synthesis of highly functionalized cyclohexanols through a cascade Michael–Henry reaction of a β-nitroolefin and a 2-(1-substituted 3-oxo-3-phenylpropyl)malononitrile. The method has the advantages of requiring mild conditions and providing a convenient workup, high diastereoselectivity, good atom economy, and a wide substrate scope, rendering it useful for the synthesis of highly functionalized cyclohexanols.

ChemInform Abstract: Organocatalyzed Michael—Henry Reactions: Enantioselective Synthesis of Cyclopentanecarbaldehydes via the Dienamine Organocatalysis of a Succinaldehyde Surrogate.

AbstractFormal [3 + 2]cycloaddition of 4‐hydroxybut‐2‐enal, a succinaldehyde surrogate, with nitroalkenes in the presence of Jorgensen—Hayashi catalyst provides cyclopentanecarbaldehydes containing 4 consecutive stereogenic centers with excellent enantioselectivities.

Preparation of novel multifunctional amino alcohols from nitroparaffins and α,β-unsaturated aldehydes

A series of novel multifunctional amino alcohols were prepared by tandem Michael–Henry reaction by reacting nitroalkanes such as 2-nitropropane with readily available α,β-unsaturated aldehydes. The dinitro compounds were further reduced by catalytic hydrogenation to obtain respective diamines. This synthetic route provides a very convenient method of preparing multifunctional amino alcohols.

Organocatalyzed Michael–Henry reactions: enantioselective synthesis of cyclopentanecarbaldehydes via the dienamine organocatalysis of a succinaldehyde surrogate

Asymmetric formal [3+2] cycloadditions of 4-hydroxybut-2-enal, a succinaldehyde surrogate, and nitroalkenes with an organocatalyst provided cyclopentanecarbaldehydes containing four consecutive stereogenic centers with excellent enantioselectivities.

New approach to the preparation of bicyclo octane derivatives via the enantioselective cascade reaction catalyzed by chiral diamine-Ni(OAc)2 complex

A highly efficient catalyst system assembled from enantiomerically pure diaminocyclohexane and Ni(OAc)(2) is, for the first time, used to catalyze the cascade Michael-Henry reaction of various diones and substituted nitroalkenes. A series of polyfunctionalized bicyclo[3.2.1]octane derivatives containing four stereogenic centers are prepared with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to 50 : 1 dr) with high yields. In addition, via this chiral diamine-Ni(OAc)(2) catalyst system, the base-induced epimerization leading to the decrease of stereoselectivity can be prevented.