Functionalized Piperidine Derivatives Research Articles

Enantioselective Dearomatization of Pyridinium Salts by Copper‐Catalyzed C4‐Selective Addition of Silicon Nucleophiles

A copper‐catalyzed C4‐selective addition of silicon nucleophiles released from an Si–B reagent to prochiral pyridinium triflates is reported. The dearomatization proceeds with excellent enantioselectivity using Cu(CH3CN)4PF6 as the precatalyst and (R,R)‐Ph‐BPE as the chiral ligand. A carbonyl group at C3 is required, likely acting a weak group to preorganize and direct the nucleophilc attack towards C4. The resulting 4‐silylated 1,4‐dihydropyridines can be further converted into functionalized piperidine derivatives.

Enantioselective Dearomatization of Pyridinium Salts by Copper-Catalyzed C4-Selective Addition of Silicon Nucleophiles.

A copper-catalyzed C4-selective addition of silicon nucleophiles released from an Si-B reagent to prochiral pyridinium triflates is reported. The dearomatization proceeds with excellent enantioselectivity using Cu(CH3CN)4PF6 as the precatalyst and (R,R)-Ph-BPE as the chiral ligand. A carbonyl group at C3 is required, likely acting a weak group to preorganize and direct the nucleophilc attack towards C4. The resulting 4-silylated 1,4-dihydropyridines can be further converted into functionalized piperidine derivatives.

Efficient synthesis of piperidine derivatives using dendrimer based catalytical pockets

AbstractThe synthesis of highly functionalized piperidine derivatives using amine functionalized maltitol‐cored dendritic polymer (MAL‐G0) in acetonitrile as the reaction medium is reported. A variety of piperidine derivatives were synthesized and the reaction gave an excellent yield of 89%–95%. The highly functionalized nature of the catalyst provided large number of active sites which resulted in good yield within a short period of time. Maltitol is a carbohydrate polyol system which was chosen here as the core for the synthesis of the dendritic catalyst; it was an effective approach for the preparation of piperidine like medicinal compounds. Maltitol‐cored dendritic polymer was effectively synthesized and characterized using GPC, TG, UV–Visible, IR, and NMR techniques and also all the synthesized piperidine derivatives were characterized using LCMS, IR, and NMR techniques.

Sulfated titania (TiO2-SO42−) as an efficient and reusable solid acid catalyst for the multi-component synthesis of highly functionalized piperidines

An efficient and one-pot procedures have been developed for the synthesis of highly functionalized piperidine derivatives via pseudo five-component reactions in the presence of sulfated titania (TiO2-SO42−) as a heterogeneous solid acid catalyst was reported for the first time. The pseudo five-component reactions of aromatic aldehydes, aromatic amines, and β-keto esters catalysed by sulfated titania (TiO2-SO42−) in methanol at 70°C provides highly functionalized piperidine derivatives in good to excellent yields. The structure as well as the relative stereochemistry of these functionalized piperidines was confirmed by melting points, IR, 1H, and 13C NMR spectral data and single crystal X-Ray analysis. This sulfated titania (TiO2-SO42−) gives an good to excellent yield with short reaction time and is inexpensive, easily recyclable catalytic material for this reaction. Higher catalytic activity of sulfated titania (TiO2-SO42−) is due to its increased Bronsted acidity.

Zirconium tetrachloride catalyzed one-pot highly efficient green synthesis of functionalized piperidines under visible light

Abstract Highly efficient multicomponent one-pot green synthesis of a series of pharmaceutically interesting functionalized piperidine derivatives has been developed based on a low-cost and eco-friendly zirconium tetrachloride catalyst via tandem reactions of 1,3-dicarbonyl compounds, aromatic aldehydes, and various amines in ethanol under visible light. High atom-economy, high yields, less reaction times, eco-friendly, and mild reaction conditions are some of the important features of this protocol. Key words: ZrCl 4 , piperidines, multi-component reactions, visible light

Densely substituted piperidines as a new class of elastase inhibitors: Synthesis and molecular modeling studies.

Elastase is the only enzyme that has the capability to degrade elastin and collagen, the two proteins essential for skin and bones. The synthesis of some densely substituted piperidines functionalized with the trifluoromethyl group (4a-j) was carried out. The newly prepared compounds were subjected to elastase enzyme inhibitory potential and antioxidant activity assays. Among the series, 4i (IC50 = 0.341 ± 0.001 μM) exhibited the maximum inhibition against elastase. Binding analysis delineated that the fluorine atom of ligand 4i showed hydrogen and hydrophobic bonds with Thr41 and Thr96, with bond distances of 3.84 and 5.631 Å, respectively. The obtained results indicate that these trifluoromethyl functionalized piperidine derivatives could be considered as potential candidates to treat skin disorders.

Calix[n]arenes: active organocatalysts for the synthesis of densely functionalized piperidines by one-pot multicomponent procedure

An efficient, suitable and high yielding method has been developed for the synthesis of different densely functionalized piperidine derivatives via pseudo-five component, one-pot domino reaction through a combination of β-ketoesters, aromatic aldehydes, and various amines using p-sulfonic acid calix[n]arenes as catalysts. The reaction was carried out in refluxing methanol, affording very good yields of the expected piperidine. Atomic economy, environmentally benign procedure, reuse of catalysts, and short reaction time are some of the important features of this protocol.

ChemInform Abstract: Silica Sulfuric Acid: An Efficient, Reusable, Heterogeneous Catalyst for the One‐Pot, Five‐Component Synthesis of Highly Functionalized Piperidine Derivatives.

Abstract20 Title compounds of type (IV) are prepared by a one‐pot three‐component reaction which is catalyzed by silica sulfuric acid.

Silica Sulfuric Acid: An Efficient, Reusable, Heterogeneous Catalyst for the One-Pot, Five-Component Synthesis of Highly Functionalized Piperidine Derivatives

A series of highly functionalized piperidine derivatives was synthesized through one-pot, five-component reaction of aldehydes, amines, and β-ketoesters. Silica sulfuric acid efficiently catalyzes the reaction to afford the corresponding piperidine derivatives in good yields. As a representative example, heating of 4-methylaninle, 4-fluorobezaldehyde, and methyl-acetoacetate in methanol in the presence of silica sulfuric acid furnished the corresponding ethyl 2,6-bis(4-fluorophenyl)-1-p-tolyl-4-(p-tolylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate in excellent yield (85%). Most of the synthesized compounds were screened in vitro for their antibacterial and antifungal activities. Most of compounds showed significant antibacterial activity.

Nanomagnetically modified ferric hydrogen sulfate (NiFe2O4@SiO2-FHS): a reusable green catalyst for the synthesis of highly functionalized piperidine derivatives

An efficient and one-pot multi-component procedure for the preparation of functionalized piperidine derivatives from reactions of aromatic aldehydes, substituted anilines and ethyl acetoacetate in the presence of ferric hydrogen sulfate-supported silica-coated magnetic nanoparticles (NiFe2O4@SiO2-FHS) as a magnetically recyclable green catalyst has been developed. The catalysts show environmentally benign character, which can be easily prepared, stored, and recovered several times without obvious significant loss of activity.

ChemInform Abstract: Tandem Aza‐Michael‐Aldol Reactions: One‐Pot Synthesis of Functionalized Piperidine Derivatives.

AbstractOptimum reaction conditions for the title reaction are examined.

ChemInform Abstract: A Facile Access to Piperidine Derivatives via Copper(I)‐Catalyzed 1,3‐Dipolar [6 + 3] Cycloadditions of Azomethine Ylides with Fulvenes.

Enantioenriched heterocyclic piperidines are important structural motifs present in numerous natural products and biologically active molecules. This article outlines our recent efforts to develop a straightforward access to highly functionalized piperidine derivatives with multiple stereogenic centers, in good yields and excellent stereoselectivities, via copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar [6+3] cycloadditions of azomethine ylides with fulvenes.

A Facile Access to Piperidine Derivatives via Copper(I)-Catalyzed 1,3-Dipolar [6+3] Cycloadditions of Azomethine Ylides with Fulvenes

Enantioenriched heterocyclic piperidines are important structural motifs present in numerous natural products and biologically active molecules. This article outlines our recent efforts to develop a straightforward access to highly functionalized piperidine derivatives with multiple stereogenic centers, in good yields and excellent stereoselectivities, via copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar [6+3] cycloadditions of azomethine ylides with fulvenes.

Tandem Aza‐Michael–Aldol Reactions: One‐Pot Synthesis of Functionalized Piperidine Derivatives

A series of novel functionalized piperidine derivatives were conveniently prepared by three‐component tandem aza‐Michael–Aldol reactions of α,β‐unsaturated enones with substituted sulfonamides in the presence of DBU. The structures of the compounds synthesized were characterized by spectral data and X‐ray crystal diffraction.

ChemInform Abstract: A Facile and Efficient Solid Supported, One‐Pot Synthesis of Functionalized Piperidine Derivatives Catalyzed by Amberlite IRA400‐Cl Resin/I2/KI via Multicomponent Reaction.

AbstractThe formation of the piperidine derivatives is assumed to proceed via reaction of the aldehyde with a β‐ketoester‐derived enolate anion to form an α‐substituted β‐ketoester intermediate.

A Facile and Efficient Solid Supported, One-Pot Synthesis of Functionalized Piperidine Derivatives Catalyzed by Amberlite IRA400-Cl Resin/I2/KI via Multicomponent Reaction

A facile and efficient one-pot, solid supported synthesis of functionalized piperidine derivatives catalyzed by Amberlite IRA400-Cl resin/I2/KI via a multicomponent reaction of various aldehydes, aromatic amines, and 1,3-dicarbonyl compounds has been achieved. The reaction has been carried out in a one-pot reaction and Amberlite resin as a solid supported catalyst at room temperature. Shorter reaction time, easy workup, yield, and mild reaction condition make the novel synthetic strategy both practical and attractive.

Acidic ionic liquids catalyzed one-pot, pseudo five-component, and diastereoselective synthesis of highly functionalized piperidine derivatives

An efficient and one-pot quantitative procedure for the preparation of functionalized piperidine derivatives from pseudo five-component reactions of aromatic aldehydes, substituted anilines, and ethyl/methyl acetoacetate (molar ratio: 2/2/1) in the presence of acidic ionic liquids such as 1-methylimidazolium hydrogen sulfate ([Hmim]HSO4), 1,1,3,3-tetramethylguanidinium perchlorate ([TMG]ClO4), and 1,1,3,3-tetramethylguanidinium trifluoroacetate ([TMG]TFA) as the catalysts has been developed. The ionic liquids were stable during the reaction process and could also be reused several times without significant loss of their activities.

ChemInform Abstract: Nickel(II) Chloride Hexahydrate as an Efficient Catalyst for the Preparation of Highly Functionalized Piperidine Derivatives.

AbstractAn efficient three‐component cyclocondensation reaction of aldehydes, aromatic amines, and acetoacetic esters leading to highly functionalized piperidines (IV) under ambient conditions is presented.

LaCl3·7H2O as an Efficient Catalyst for One-Pot Synthesis of Highly Functionalized Piperidines via Multi-component Organic Reactions

The three-component one-pot synthesis of highly functionalized piperidine derivatives was carried out by condensing 1,3-dicarbonyl compounds with aromatic aldehydes and aniline using a catalytic amount (10 mol%) of LaCl3·7H2O in methanol at room temperature. The main features of current protocol include easy work up, mild reaction conditions, good yields and high atom economy.

Bismuth nitrate-catalyzed multicomponent reaction for efficient and one-pot synthesis of densely functionalized piperidine scaffolds at room temperature

A simple, straightforward, and highly efficient diastereoselective multicomponent one-pot synthesis of a series of pharmaceutically interesting functionalized piperidine derivatives has been developed based on a low-cost and environmentally benign Bi(NO3)3·5H2O catalyst via tandem reactions of 1,3-dicarbonyl compounds, aromatic aldehydes, and various amines in ethanol at room temperature. High atom-economy, good yields, eco-friendliness, and mild reaction conditions are some of the important features of this protocol.