Tandem Michael-Henry Reaction Research Articles

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).

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.

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: 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).

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.

Enantioselective synthesis of bicylco[3.2.1]octan-8-ones using a tandem Michael–Henry reaction

Bicyclo[3.2.1]octan-8-ones have been prepared from a tandem Michael–Henry reaction between cyclohexane-1,2-diones and nitroalkenes using a quinine-derived thiourea as the catalyst. Although four stereogenic centers were created during the reaction, only two diastereomers were obtained in good diastereoselectivity and high enantioselectivity (92–99% ee). When 3-methylcyclohexane-1,2-dione (R 1=Me) was used as the substrate, only the regioisomeric product of the corresponding thermodynamic enolate was obtained.

ChemInform Abstract: Synthesis of 2,3,4‐Trisubstituted Thiochromans Using an Organocatalytic Enantioselective Tandem Michael—Henry Reaction

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Organocatalytic Asymmetric Tandem Michael−Henry Reactions: A Highly Stereoselective Synthesis of Multifunctionalized Cyclohexanes with Two Quaternary Stereocenters

A novel organocatalytic asymmetric tandem Michael-Henry reaction catalyzed by 9-amino-9-deoxyepiquinine (VI) has been developed. The reaction was efficiently catalyzed by catalyst VI to give highly functionalized cyclohexanes with four stereogenic carbons including two quaternary stereocenters in excellent enantioselectivities (97 to >99% ee) and high diastereoselectivities (93:7-99:1 dr). Thus, the first organocatalytic asymmetric Henry reaction of common ketones as acceptors is shown.

Synthesis of 2,3,4-Trisubstituted Thiochromanes using an Organocatalytic Enantioselective Tandem Michael-Henry Reaction.

Enantioenriched 2,3,4-trisubstituted thiochromanes have been synthesized by using a cupreine-catalyzed tandem Michael addition-Henry reaction between 2-mercaptobenzaldehydes and β-nitrostyrenes. Good diastereoselectivities and enantioselectivities were obtained for the title compounds, which may be further improved through a single recrystallization (up to 98% de and> 99% ee).

Organocatalytic Asymmetric Tandem Michael-Henry Reaction

An organocatalytic asymmetric tandem reaction for the construction of highly functionalized cyclohexane carbaldehydes is described. Chiral α,α-diphenylprolinol silyl ether 1 (10 mol%) mediates a Michael addition of pentane-1,5-dial (3) to nitroolefins 2 followed by an intra­molecular Henry reaction to give products of type 4 in good yields, diastereoselectivities and excellent enantioselectivities. Two C-C bonds and four stereocenters are generated in the process.

Enantiodivergent synthesis of 2-hydroxymethyl-3-hydroxy-4-nitro-pyrrolidines through tandem Michael-Henry reaction using L-serine as the chiral educt

By utilizing L-serine, both enantiomers of all trans 2-hydroxymethyl-3-hydroxy-4-nitro-pyrrolidine were efficiently prepared through tandem Michael-Henry methodology. Their stereochemistry has been assigned through conversion of one of them to trans 2-hydroxymethyl-3-hydroxypyrrolidine, a naturally occurring compound recently isolated from Castanospermum australe.

A one-pot synthesis of nitrohydroxylated pyrrolidine and piperidine ring systems by tandem Michael-Henry reaction

Nitrohydroxylated pyrrolidine and piperidine ring systems are conveniently obtained through a one-pot procedure involving sequential Michael-Henry reaction between nitroethylene and a nitrogen nucleophile incorporating a suitably placed precursor for the generation either reductively or oxidatively of an aldehyde group which is directly trapped in the subsequent nitroaldolization step.