Iron-catalyzed aminolysis of β-carbonyl 1,3-dithianes: synthesis of stereodefined β-enaminones and 3,4-disubstituted pyrazoles

A novel iron-catalyzed aminolysis of β-carbonyl 1,3-dithianes with various amines including ammonia, primary and secondary amines, as well as hydrazine hydrate has been developed, leading to the synthesis of stereodefined β-enaminones and 3,4-disubstituted pyrazoles in good to high yields.     

Efficient synthesis of β-enaminones and β-enaminoesters catalyzed by gold (I)/silver (I) under solvent-free conditions

An efficient method for the synthesis of β-enaminones and β-enaminoesters using a combination of [(PPh(3))AuCl]/AgOTf as catalyst has been developed. The reaction between 1,3-dicarbonyl compounds and primary amines was carried out under solvent-free conditions with low catalyst loading in good to excellent yields at room temperature.     

A new approach for the synthesis of spiro and gem-dimethyl-substituted 1,4-oxazepines from N-propargylic β-enaminones

An efficient and general method for the synthesis of spiro-1,4-oxazepines and 3,3-dimethyl-1,4-oxazepines is reported. When treated with ZnI₂ and AgSbF₆ in refluxing DCE, cyclohexane-embedded N-propargylic β-enaminones underwent 7-exo-dig cyclization to afford spiro-1,4-oxazepines, specifically 12-methylene-11-oxa-7-azaspiro[5.6]dodeca-7,9-dienes, in good to high yields. Accordingly, N-(1,1-dimethyl)propargylic β-enaminones produced 3,3-dimethyl-1,4-oxazepines. Cyclization was found to be general for a diverse range of N-propargylic β-enaminones with high efficiency and broad functional group tolerance. This operationally easy method might provide quick access to a library of functionalized spiro and gem-dimethyl-substituted 1,4-oxazepine derivatives of pharmacological interest.     

An ionic liquid as reaction medium for the synthesis of halo-containing β-enaminones at room temperature

A series of twenty halomethylated β-enaminones [RC(O)CH=C(R ¹)NR ³ R ⁴, where R = CF₃,CCl₃, CHCl₂; R ¹ = H, Me, Ph; R ³ = H, Me, Bu, Et; R ⁴ = Me, Et, Bu, allyl, tert-amyl, CH₂CH₂OH, Bn, Ph] were synthesized using the ionic liquid [bmim]BF₄ at room temperature. It is demonstrated that this ionic liquid is a reaction medium suitable for the amination of β-alkoxyvinyl halomethyl ketones. The advantages of this method are the absence of solvents, short reaction times, and good yields. Correspondence: Marcos A. P. Martins, Núcleo de Química de Heterociclos – NUQUIMHE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.     

Silica-supported LiHSO4 as a highly efficient, heterogeneous and reusable catalytic system for the solvent-free synthesis of β-enaminones and β-enamino esters

A highly efficient, simple and green procedure for the synthesis of β-enaminones and β-enamino esters is described. The reaction of aromatic and aliphatic amines with β-dicarbonyl compounds using catalytic amount of silica-supported LiHSO₄ (LiHSO₄/SiO₂) under solvent-free conditions at 80 °C affords the title compounds in high to excellent yields and in short reaction times.     

Gold(III) N-heterocyclic carbene complexes mediated synthesis of β-enaminones from 1,3-dicarbonyl compounds and aliphatic amines

A series of gold(III) N-heterocyclic carbene complexes [1-(R(1))-3-(R(2))imidazol-2-ylidene]AuBr(3) [R(1) = i-Pr, R(2) = CH(2)Ph (1c); R(1) = mesityl, R(2) = CH(2)Ph (2c); R(1) = i-Pr, R(2) = CH(2)COt-Bu (3c), and R(1) = t-Bu, R(2) = CH(2)COt-Bu (4c)] act as effective precatalysts in the synthesis of β-enaminones from 1,3-dicarbonyl compounds and primary amines under ambient conditions. Specifically the 1c-4c complexes efficiently catalyzed the condensation of a variety of cyclic as well as acyclic 1,3-dicarbonyl compounds, namely, acetyl acetone, benzoylacetone, 2-acetylcyclopentanone, and ethyl-2-oxocyclopentanecarboxylate with primary aliphatic amines, viz., methylamine, ethylamine, n-propylamine, i-propylamine, and n-butylamine, yielding β-enamines at room temperature. Interestingly enough, the more electrophilic gold(III) 1c-4c complexes exhibited superior activity in comparison to the gold(I) counterparts 1b-4b. A comparison along a representative 4a-c series further underscored the importance of gold in the reaction as both the gold(I) 4b and gold(III) 4c complexes were more effective than the silver analogue 4a. The density functional theory (DFT) study revealed that the strong σ-donating nature of the N-heterocyclic carbene ligand results in a strong C(carbene)-Au(III) interaction in the 1c-4c complexes.     

Highly stereoselective synthesis of cis-β-enaminones mediated by diethyl azodicarboxylate

Promoted by diethyl azodicarboxylate, a novel and highly stereoselective synthesis of cis-β-enaminones via oxidative dehydrogenation and hydration of the substituted propargylamines was realized. The possible mechanism was also proposed.     

Preparation,characterization and catalytic activity of MoO3/CeO2–ZrO2 solid heterogeneous catalyst for the synthesis of β-enaminones

A series of CeO₂–ZrO₂ with different molybdenum (8–20 wt% MoO₃) loaded materials were prepared by homogeneous co-precipitation followed by impregnation method. The prepared materials were tested for their catalytic activity performance in the synthesis of β-enaminones by condensation of various anilines with dimedone under solvent-free conditions in microwave providing excellent yields within short reaction time. An obtained result reveals that, catalytic activity increases with increase in Mo wt% loading. The particle size of prepared materials was estimated using Debye–Scherrer equation. Particle size increases with increase in Mo wt% loading providing nanosized particle ranging from 7.11 to 42.09 nm. The synthesized materials were characterized by means of X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) techniques.     

Stereochemistry in alkylations of dianions of β-hydroxysulfoxides and β-hydroxysulfones

Alkylations of dianions of β-hydroxysulfoxides and β-hydroxysulfones have been found to be affected by chelation of a Li cation with a sulfinyl group and by coordination of the cation with tetrahydrofuran rather than a sulfonyl group, respectively.     

Influence of β-substituents in aldol reactions of boron enolates of β-alkoxy methylketones

Moderate to good levels of substrate-based 1,5-syn-stereocontrol could be achieved in the boron-mediated aldol reactions of β-tert-butyl methylketones with achiral aldehydes, independent of the nature of the β-alkoxy protecting group (P = PMB or TBS). The analysis of the relative energies of the transition structures by theoretical calculations using the density functional B3LYP shows relative energies favoring the corresponding OUT-1,5-SYN transition structures, explaining the observed 1,5-syn stereoinduction.     

Structure determination of glycopeptide of β-momorcharin

The structure of the N-linked oligosaccharide chain of β-momorcharin, a ribosome-inactivating protein from the seeds of Momordica charantia Linn (Cucurbitaceae), was determined. A glycopeptide liberated by pronase digestion of the glycoprotein was subjected to amino acid and neutral carbohydrate analysis to establish the composition of amino acid and sugar residues. The sequences and glycosylation hnkages of the sugar and amino acid residues in the glycopeptide were determined as Manαl-6(XyIβ1-2)-Manβ1-4GlcNAcβ1-4(Fucαl-3)-GlcNAc-Asn-Leu by 2D-NMR spectroscopy and FAB-MS data.     

Preparation of β-fluoro- and β,β-difluoro-histidinols

Nucleophilic attack of azide on 2-bromo-3-fluoro-3-(1-trityl-1H-imidazol-4-yl)-propan-1-ol (1a) in aprotic solvent occurs on the 2-position to give the 2-azido derivative (2a). Reduction of azide and removal of the trityl group produces β-fluorohistidinol (6a). Elimination of HBr from 1a followed by “FBr” addition to the resulting double bond gives 2-bromo-3,3-difluoro-3-(1-trityl-1H-imidazol-4-yl)-propan-1-ol (1b). Nucleophilic attack of azide followed by reduction and removal of the trityl group, as for the preparation of 6a, gives β,β-difluorohistidinol (6b). Initial attempts, under a variety of conditions, to oxidize the fluorinated histidinol precursors to carboxylic acids have not been successful.     

Synthesis of Unsymmetrical β-Arylaminoketones

Azomethines derived from aniline were condensed with acetophenone derivatives to obtain new unsymmetrical -arylaminoketones.     

Regioselective Acetylation of β-Cyclodextrin

One-stage methods of synthesis of water-soluble -cyclodextrins selectively acetylated by primary or secondary hydroxy groups have been found, that make use of acetyl chloride and hydrogen chloride acceptors of different nature.     

New Synthesis of β-Iodostyrenes

A general procedure for the synthesis of -iodostyrenes is proposed. Aromatic aldehyde and ketone hydrazones are converted into the corresponding -iodostyrenes by treatment with CHI₃ in the presence of a catalytic amount of CuCl.     

Selective synthesis of β-alkylpyrroles

β-Alkylpyrroles are key structural motifs found in many natural products and biologically active compounds as well as functional organic materials. For this reason, synthetic chemists continue to be interested in construction of the framework of β-alkylpyrroles. Due to sufficient aromaticity and π-excessive nature of pyrroles, a straightforward approach to β-alkylpyrroles should be electrophilic aromatic substitution (S(E)Ar) toward the pyrrole ring. However, since a primary nucleophilic site of pyrroles is an α-position, some "trick" is required to direct incoming alkyl electrophiles toward a β-position. This Concept article focuses on presenting previous efforts that have been devoted to the synthesis of β-alkylpyrroles, mainly through the S(E)Ar route.     

Adamantylation of β-dicarbonyl compounds

Reactions of adamantan-1-ol with β-dicarbonyl compounds in 1,2-dichloroethane in the presence of In(OTf)₃, Ga(OTf)₃, Sc(OTf)₃, or Cu(OTf)₂ give the corresponding adamantylated derivatives in 45–93% yields.