Addition Of Diethyl Malonate Research Articles

Reaction of β-Nitrostyrene with Diethyl Malonate in the Presence of Bispidines: The Unusual Role of the Organocatalyst

The aim of this work was the investigation of novel organocatalysts for the Michael addition of diethyl malonate to β-nitrostyrene. The methodology of the study included NMR titration, reaction monitoring by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS), product characterization by MALDI, IR spectroscopy, scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and elemental analysis. As a result, evidence of supramolecular interactions between two pairs of components of the reaction was found. In addition to the supramolecular complexes, an unusual reaction, i.e., the Michael addition of NH-bispidines to β-nitrostyrene, was found, which led to previously unknown oligomers of β-nitrostyrene. A new mechanism for the catalytic action of NH-bispidine was proposed, which involved catalysis not by the initial organocatalyst but rather by its adduct with β-nitrostyrene. Thus, in this reaction, N-benzylbispidine acted as an initiator, and the real catalyst was the betaine formed during the initiation stage.

A convenient one-pot synthesis, theoretical studies, and NMR-based conformational analysis of nitroarylidene dimalonates

Tandem Knoevenagel-Michael addition of diethyl malonate to nitro-substituted benzaldehydes was found to proceed in a mild and convenient process. The 1H NMR spectra of the products showed significant changes according to the position of the nitro group. Conformational analysis calculations confirmed that in all cases, a structure containing a mirror plane occurred at energies near the ground state. However, for the meta and ortho substituted products, increased steric crowding resulted in decreased rotational freedom of the ethyl substituents. Consistent with the observation of increased steric stress, molecular orbital calculations predicted a higher electrophilic reactivity of the ortho nitro substituted product.

Nitroalkenes in the Ni(II) Catalyzed Asymmetric Michael Addition. Convenient Route to the Key Intermediate of Brivaracetam

AbstractA series of Ni(II) complexes with novel chiral ligands derived from (1R,2R)‐1,2‐diphenylethane‐1,2‐diamine was synthesized. The catalytic activity of these complexes in the asymmetric Michael reaction is demonstrated. Asymmetric addition of diethyl malonate to ω‐nitrostyrene and 1‐nitropent‐1‐ene in the presence of these complexes leads to the enantiomerically enriched diethyl (S)‐2‐(2‐nitro‐1‐phenylethyl)malonate (up to 96 % ee) and (R)‐diethyl 2‐(1‐nitropenthan‐2‐yl)malonate (up to 91 % ee). (4R)‐4‐Propylpyrrolidin‐2‐one, the key intermediate of antiepileptic drug brivaracetam, was obtained from the corresponding nitroester.

Synthesis of Nonracemic Tetrazole GABA Analogs

Nonracemic 3-substituted 4-(1H-tetrazol-1-yl)butanoic acids, analogs of the neurotropic drugs phenibut, tolibut, and baclofen, were synthesized by a three-component reaction of the R-isomers of the corresponding amino acids, triethyl orthoformate, and sodium azide. The key stage of the synthesis is the asymmetric addition of diethyl malonate to nitroalkenes, catalyzed by a Ni(II) complex of (S,S)-N,N′-dibenzylcyclohexane-1,2-diamine.

Asymmetric Synthesis of Adamantyl GABA Analogues

An efficient synthesis of (R)- and (S)-4-amino-3-(adamant-1-yl)butyric acids and (R)- and (S)-4-(adamant-1-yl)pyrrolidin-2-ones is presented. The synthetic strategy is based on asymmetric Michael addition of diethyl malonate to 1-(adamant-1-yl)-2-nitroethene using available Ni(II) complex as the catalyst. The procedures provide good to high enantioselectivity of Michael addition to sterically hindered nitroalkene and good yields of (R)- and (S)-enantiomers of 3-adamantyl substituted GABA.

Enantioselective Michael Addition of Diethyl Malonate on Substituted Chalcone Catalysed by Nickel-Sparteine Complex

A series of transition metal with Sparteine a novel chiral catalyst was facilely synthesized, all of which contain a chiral Sparteine unit as a bidentate ligand. These bidentate chiral auxiliaries were found to be an efficient chiral catalyst in nickel-mediated, enantioselective Michael addition of Diethyl malonate to substituted chalcone. The corresponding adducts were obtained in good yields (80-91%) under simple and clean reaction condition.

A mechanistic study of the Lewis acid–Brønsted base–Brønsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone

Reaction shown to exhibit biomimetic behaviour.

Stereoselective Synthesis of Dipeptidyl Peptidase‐4 (DPP‐4) Inhibitor, (R)‐Sitagliptin

AbstractAn operationally simple and efficient strategy for a highly potent Dipeptidyl Peptidase‐4 (DPP‐4) inhibitor, sitagliptin has been developed employing readily available precursors. The chiral β‐amino acid core of sitagliptin has been constructed through a Barbier type allylation of chiral sulfinyl imine or a Mannich type addition of diethyl malonate. This approach is more convenient, exquisitely selective and practical.

Multigram synthesis of an advanced nitroalkene intermediate: application in synthesis of octahydroindol-2-one derivative featuring diastereoselective Michael addition of diethylmalonate

Gram scale synthesis of a novel nitrocyclohexenetriol derivative is reported by applying intramolecular Henry reaction as a key step. Searching the utility of this scaffold, synthesis of hydroxylated octahydroindol-2-one derivative, which is a backbone of many amaryllidaceae alkaloids was also achieved via a very diastereoselective Michael addition of diethylmalonate to hydroxylated nitrocyclohexenetriol.

Optically active helical polymers with pendent thiourea groups: Chiral organocatalyst for asymmetric michael addition reaction

ABSTRACTThis article reports a novel category of helical substituted polyacetylenes bearing pendant thiourea groups and showing remarkable asymmetric catalysis ability. Thiourea‐based monomer and another chiral monomer underwent copolymerization, affording copolymers with considerable optical activity. The copolymers were used as chiral organocatalyst to homogeneously catalyze the asymmetric Michael addition of diethyl malonate to trans‐β‐nitrostyrene. During catalysis, a synergetic effect occurred between the pendant thiourea moieties and the helical structures in the polymer backbones. The enantioselectivity of the reaction was governed by the thiourea moieties. Meanwhile, the concaves along the helices provided specific domains where the substrates and catalytic groups were packed together, leading to a remarkable enhancement of product yield and enantioselectivity. Product with high yield (85%) and satisfactory ee (up to 72%) can be obtained. The present helical polymers open up new opportunities for developing macromolecules as mimetic enzymes catalyzing asymmetric reactions. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1816–1823

Electrochemical generation of a catalyst for Michael addition of dicarbonyl compounds and cyanide anion to acryloylferrocene

Michael addition of diethyl malonate, ethyl acetoacetate, acetylacetone, and cyanide anion to acryloylferrocene promoted by a catalyst in situ generated from a sacrificial zirconium anode is described. Most of the obtained compounds were identified by comparison of their spectral and physical data with those published elsewhere, whereas the only newly synthesized compound - diethyl 2,2-bis(3-ferrocenyl-3-oxopropyl)malonate - was completely characterized by spectral (IR, 1H- and 13C-NMR), physical and crystallographic (single-crystal X-ray) data.

ChemInform Abstract: Highly Enantioselective Michael Addition of Diethyl Malonate to Chalcones Catalyzed by Cinchona Alkaloids‐Derivatived Bifunctional Tertiary Amine‐Thioureas Bearing Multiple Hydrogen‐Bonding Donors.

AbstractBoth catalysts used show excellent catalytic activities and enantioselectivities, giving the (R)‐ and (S)‐enantiomers of the adducts.

Enantioselective Michael addition of malonates to aromatic nitroalkenes catalyzed by monosaccharide-based chiral crown ethers

The asymmetric Michael addition of diethyl malonate and α-substituted diethyl malonates to aromatic nitroalkenes was carried out under mild reaction conditions in a solid–liquid phase transfer reaction in the presence of α-d-glucopyranoside- and α-d-mannopyranoside-based crown ethers as the catalysts. The use of d-glucose-based lariat ether 1 gave the best results. The substituents of the β-nitrostyrene and the diethyl malonate had a significant impact on the chemical yields and enantioselectivity. The addition of diethyl-2-acetamidomalonate to aromatic nitroalkenes afforded the corresponding Michael adducts in moderate to high enantiomeric excess (ee up to 99%). The reaction of diethyl-2-methylmalonate with 2-nitro-β-nitrostyrene gave the adduct with 93% enantiomeric excess in the presence of crown catalyst 1.

Highly enantioselective Michael addition of diethyl malonate to chalcones catalyzed by cinchona alkaloids-derivatived bifunctional tertiary amine-thioureas bearing multiple hydrogen-bonding donors

Chalcones are still challenge substrates in Michael reactions, and only limited success has been achieved. This work describes a highly enantioselective Michael addition of diethyl malonate with chalcones catalyzed by cinchona alkaloids-derivatived bifunctional tertiary amine-thioureas bearing multiple hydrogen-bonding donors.

ChemInform Abstract: Imidazolium‐Based Organic—Inorganic Hybrid Silica as a Functional Platform Dramatically Boosts Chiral Organometallics Performance in Asymmetric Catalysis.

AbstractChiral rhodium and nickel catalysts immobilized on a phase‐transfer featured, imidazolium‐based, organic‐inorganic hybrid silica are applied to the asymmetric transfer hydrogenation of ketones and the asymmetric Michael addition of diethyl malonate.

Enantioselective synthesis of γ-aminobutyric acid derivatives by Ni(II)-catalyzed reaction of diethyl malonate with nitroalkenes

A new synthetic approach to (3R)-4-amino-3-methylbutyric acid and [(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide [(R)-phenotropil] has been developed. Asymmetric center with a required configuration has been generated via enantioselective addition of diethyl malonate to 1-nitropropene and β-nitrostyrene, catalyzed by Ni(II) complexes with (R,R)- and (S,S)-N,N′-dibenzylcyclohexane-1,2-diamine.

Reaction of ω-nitrostyrene with diethyl malonate in the presence of chiral nickel(II) complexes

Single-ligand complexes of nickel(II) with chiral diamines based on L-proline and (S)-camphor efficiently catalyze addition of diethyl malonate to ω-nitrostyrene in the presence of 1 equiv of triethylamine as co-catalyst. The reaction enantioselectivity depends on the chiral ligand structure.

ChemInform Abstract: Chemoenzymatic Preparation of Optically Active 3‐(1H‐Imidazol‐1‐yl)cyclohexanol‐based Ionic Liquids: Application in Organocatalysis and Toxicity Studies.

AbstractNewly synthesized enantiopure imidazolium salts (VII) are used as chiral phase‐transfer catalysts in the Michael addition of diethyl malonate (IX) to trans‐chalcone (VIII) giving the corresponding adduct (X) albeit with very poor enantioselectivity.

Enantioselective addition of diethyl malonate to ω-nitrostyrenes in the presence of cobalt and manganese complexes with N,N′-dibenzyl-(1S,2S)-cyclohexane-1,2-diamine

Enantioselective addition of diethyl malonate to nitrostyrene and para-chloronitrostyrene is catalyzed by cobalt and manganese complexes with N,N′-dibenzyl-(1S,2S)-cyclohexane-1,2-diamine generated in situ. Enantiomeric excess of the (R)-isomers in the reaction products is 66–87%.

ChemInform Abstract: Chiral 2‐Aminobenzimidazole Bifunctional Organocatalysts: Effect of Di‐CF3 and TFA on Catalytic Mechanisms.

AbstractBIM is synthesized and applied to Michael addition of diethyl malonate to nitroolefins.