One-pot five-component high diastereoselective synthesis of polysubstituted 2-piperidinones from aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate

Vereshchagin, Anatoly N.; Karpenko, Kirill A.; Elinson, Michaïl N.; Minaeva, Alexandra P.; Goloveshkin, Alexander S.; Hansford, Karl A.; Egorov, Mikhail P.

doi:10.1007/s11030-019-09997-6

Cited by 12 publications

(7 citation statements)

References 43 publications

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“…Vereshchagin and co-workers developed a reaction using two equiv of aryl aldehydes and one equiv each of dialkylmalonates, malononitrile or alkyl cyanoacetate, and ammonium acetate or ammonia for the synthesis of 2-piperidinone derivatives 51 or 52 (Scheme 19) [29]. The reaction involves Knoevenagel condensation of aryl aldehydes with malononitrile or alkyl cyanoacetate followed by Michael addition of dialkylmalonates to afford intermediates 53.…”

Section: X For Peer Reviewmentioning

confidence: 99%

“…The Adib lab developed a method for the synthesis of 3-oxacyclobuta[cd]pentalenes 54 using two equiv of dialkyl acetylenedicarboxylates and one equiv each of phenacyl bromides, malononitrile and isocyanides at ambient temperature in absolute ethanol (Scheme 20) [30]. The phenacyl bromides undergo nucleophilic substitution with malononitrile in the presence of Et3N to form malononitriles 55 for the reaction with zwitterionic intermediates 56 which are generated in situ from the reaction of the isocyanides and the Vereshchagin and co-workers developed a reaction using two equiv of aryl aldehydes and one equiv each of dialkylmalonates, malononitrile or alkyl cyanoacetate, and ammonium acetate or ammonia for the synthesis of 2-piperidinone derivatives 51 or 52 (Scheme 19) [29]. The reaction involves Knoevenagel condensation of aryl aldehydes with malononitrile or alkyl cyanoacetate followed by Michael addition of dialkylmalonates to afford intermediates 53.…”

Section: X For Peer Reviewmentioning

confidence: 99%

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Recent Developments on Five-Component Reactions

Zhi

Zhang

2021

Molecules

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Multicomponent reactions (MCRs) have inherent advantages in pot, atom, and step economy (PASE). This important green synthetic approach has gained increasing attention due to high efficiency, minimal waste, saving resources, and straightforward procedures. Presented in this review article are the recent development on 5-compoment reactions (5CRs) of the following six types: (I) five different molecules A + B + C + D + E; pseudo-5CRs including (II) 2A + B + C + D, (III) 2A + 2B + C, (IV) 3A + B + C, (V) 3A + 2B, and (VI) 4A + B. 5CRs with more than five-reaction centers are also included.

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Section: X For Peer Reviewmentioning

confidence: 99%

Section: X For Peer Reviewmentioning

confidence: 99%

Recent Developments on Five-Component Reactions

Zhi

Zhang

2021

Molecules

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“…Earlier, we developed effective methods of diastereoselective multicomponent synthesis of substituted piperidines, where ammonium acetate was used as a nitrogen source for the piperidine ring formation [21][22][23][24][25]. In this research, we have developed the rst example of an effective highly selective fourcomponent synthesis of pyridinium salts of piperidin-2-ones from simple and available reagents.…”

Section: Introductionmentioning

confidence: 99%

Highly diastereoselective synthesis of piperidine-2-one-substituted pyridinium salts from pyridinium ylides, aldehydes, Michael acceptors and ammonium acetate

Vinokurov¹,

Iliyasov²,

Karpenko³

et al. 2023

Preprint

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A novel four-component diastereoselective synthesis of pyridinium salts of piperidin-2-ones is reported. The Michael–Mannich cascade was conducted using Michael acceptors, pyridinium ylides, aromatic aldehydes and ammonium acetate in methanol. It is a convenient approach to the synthesis of 1-((3SR,4RS,6SR)-5,5-dicyano-2-oxo-4,6-diarylpiperidin-3-yl)pyridin-1-ium halogenides with three stereocenters in 48–84% or 1-((3SR,4RS,5RS,6SR)-5-cyano-5-(methoxycarbonyl)-2-oxo-4,6-diarylpiperidin-3-yl)pyridin-1-ium halogenide with four stereocenters in 44–74%. This reaction is highly stereoselective. Only one diastereomer was formed. Ammonium acetate plays a dual role, acting as a base and as a nitrogen source. Structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, IR and mass spectra. The formation of a single diastereomer was confirmed by singe-crystal X-ray diffraction studies.

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“…We have carried out the multicomponent synthesis of substituted piperidines [ 41 , 42 , 43 , 44 , 45 ]. Ammonium acetate or aqueous ammonia were the nitrogen sources for piperidine cycles.…”

Section: Introductionmentioning

confidence: 99%

Tetrahydropyridines’ Stereoselective Formation, How Lockdown Assisted in the Identification of the Features of Its Mechanism

Vereshchagin¹,

Iliyasov²,

Karpenko³

et al. 2022

Molecules

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The multicomponent reaction of aldehydes, cyano-containing C-H acids, esters of 3-oxocarboxylic acid and ammonium acetate led to unexpected results. The boiling of starting materials in methanol for one to two hours resulted in the formation of polysubstituted 1,4,5,6-tetrahydropyridines with two or three stereogenic centers. During the 2020 lockdown, we obtained key intermediates of this six-step domino reaction. A number of fast and slow reactions occurred during the prolonged stirring of the reaction mass at rt. Sequence: 1. Knoevenagel condensation; 2. Michael addition; 3. Mannich reaction; 4. cyclization—fast reactions and cyclization of the product polysubstituted 2-hydroxypiperidine—was isolated after 40 min stirring at rt. Further monitoring proved the slow dehydration of 2-hydroxypiperidine to obtain 3,4,5,6-tetrahydropyridine after 7 days. Then, four-month isomerization occurred with 1,4,5,6-tetrahydropyridine formation. All reactions were stereoselective. Key intermediates and products structures were verified by X-ray diffraction analysis. Additionally, we specified conditions for the selective intermediates’ preparation.

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One-pot five-component high diastereoselective synthesis of polysubstituted 2-piperidinones from aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate

Cited by 12 publications

References 43 publications

Recent Developments on Five-Component Reactions

Recent Developments on Five-Component Reactions

Highly diastereoselective synthesis of piperidine-2-one-substituted pyridinium salts from pyridinium ylides, aldehydes, Michael acceptors and ammonium acetate

Tetrahydropyridines’ Stereoselective Formation, How Lockdown Assisted in the Identification of the Features of Its Mechanism

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