Divergent synthesis of dual 1,4-dihydropyridines with different substituted patterns from enaminones and aldehydes through domino reactions

A concise and efficient protocol for the regioselective synthesis of dual 1,4-dihydropyridines with several substituted patterns has been developed from a cascade cyclization of enaminones and aldehydes in different media (EtOH/CH₃CN). The one-pot cascade reaction involves at least five reactive sites and generates multiple C–C and C–N bonds. The established protocol explores the chemistry of enaminones by employing their three reactive sites. The method has several advantages including mild conditions, operational simplicity, and high bond-forming efficiency. It may offer promise in a variety of biochemical applications.

A concise and efficient protocol for the regioselective synthesis of dual 1,4-dihydropyridines with several substituted patterns has been developed from a cascade cyclization of enaminones and aldehydes in different media (EtOH/CH₃CN).     

Iodine-catalyzed efficient synthesis of xanthene/thioxanthene-indole derivatives under mild conditions

An iodine-catalyzed nucleophilic substitution reaction of xanthen-9-ol and thioxanthen-9-ol with indoles has been developed, providing an efficient procedure for the synthesis of xanthene/thioxanthene-indole derivatives with good to excellent yields. This protocol offers several advantages, such as short reaction times, green solvent, operational simplicity, easily available catalyst and mild reaction conditions. Moreover, this method showed good tolerance of functional groups and a wide range of substrates.

An efficient synthesis of xanthene/thioxanthene-indole derivatives has been developed through iodine-catalyzed nucleophilic substitution reaction of xanthen-9-ols and thioxanthen-9-ol with indoles.     

DIBALH: from known fundamental to an unusual reaction; chemoselective partial reduction of tertiary amides in the presence of esters

This study presents a quick and reliable approach to the chemoselective partial reduction of tertiary amides to aldehydes in the presence of readily reducible ester groups using commercial DIBALH reagent. Moreover, the developed method was also extended to multi-functional molecules bearing ester moieties, which were successfully chemoselectively reduced to the corresponding aldehydes.

Highly chemoselective partial reduction of tertiary amides to aldehydes over esters are reported with commercial DIBALH. Various aldehydes are synthesized in excellent yields.     

Synthesis of highly substituted tetrahydroquinolines using ethyl cyanoacetate via aza-Michael–Michael addition

A three-component cascade reaction involving 2-alkenyl aniline, aldehydes, and ethyl cyanoacetate in the presence of DBU to synthesize highly substituted 1,2,3,4-tetrahydroquinolines is reported. The reaction proceeded through the Knoevenagel condensation of ethyl cyanoacetate with aldehydes followed by the aza-Michael–Michael addition with 2-alkenyl anilines to prepare the tetrahydroquinoline scaffolds.

A three-component cascade reaction involving 2-alkenyl aniline, aldehydes, and ethyl cyanoacetate in the presence of DBU to synthesize highly substituted 1,2,3,4-tetrahydroquinolines is reported.     

Bis-indolylation of aldehydes and ketones using silica-supported FeCl3: molecular docking studies of bisindoles by targeting SARS-CoV-2 main protease binding sites

We report herein an operationally simple, efficient and versatile procedure for the synthesis of bis-indolylmethanes via the reaction of indoles with aldehydes or ketones in the presence of silica-supported ferric chloride under grindstone conditions. The prepared supported catalyst was characterized by SEM and EDX spectroscopy. The present protocol has several advantages such as shorter reaction time, high yield, avoidance of using harmful organic solvents during the reaction and tolerance of a wide range of functional groups. Molecular docking studies targeted toward the binding site of SARS-CoV-2 main protease (3CL^pro or M^pro) enzymes were investigated with the synthesized bis-indoles. Our study revealed that some of the synthesized compounds have potentiality to inhibit the SARS-CoV-2 M^pro enzyme by interacting with key amino acid residues of the active sites via hydrophobic as well as hydrogen bonding interactions.

Silica supported FeCl₃ catalyzed simple protocol for the synthesis of bis-indolylmethanes was explored via grindstone chemistry. Synthesized compounds were screened virtually as inhibitor by targeting the binding site of SARS-CoV-2 main protease enzyme.     

Chlorotrifluoroethylidenes: an efficient and convenient approach to their synthesis

A convenient one step synthesis of chlorotrifluoroalkyl olefins starting from aldehydes was developed. The stable reagent 2-((1-chloro-2,2,2-trifluoroethyl)sulfonyl)benzothiazole was prepared from readily available benzothiazole-2-thiol and halothane. This method comprises using stable 2-((1-chloro-2,2,2-trifluoroethyl)sulfonyl)benzothiazole according to the Julia procedure and presents new opportunities for the synthesis of trifluoroalkylidene derivatives.

A convenient one step synthesis of chlorotrifluoroalkyl olefins starting from aldehydes was developed.     

Spectroscopic demonstration of sinapic acid methyl ester complexes with serum albumins

The methyl ester of sinapic acid (MESA) is a molecule with confirmed antioxidant properties. It is important to establish whether it can be transported across humans and animals. Therefore, we investigated MESA interactions with serum albumins, namely, human serum albumin (HSA), bovine serum albumin (BSA), rabbit serum albumin (RSA), and sheep serum albumin (SSA). Experiments were performed in a pH range from 5.9 to 10.7 using absorption and fluorescence techniques. It was found that MESA formed complexes with every albumin in the entire pH range under examination, which was confirmed by the appearances of new absorption and fluorescence complex bands. Fluorescence intensities were much higher (up to 20 times) and lifetimes were up to 340 times as compared to those for unbound MESA. The quenching experiments at pH 7.4 showed that the stoichiometry for every albumin was 1 : 1; the binding constant was the highest for HSA, which reached 52 000 M⁻¹. The obtained results suggested that MESA preferred the hydrophobic binding sites in albumins. The analysis of the fluorescence spectra and fluorescence lifetimes showed two possibly different binding sites in BSA, RSA, and SSA as well as three binding sites in HSA.

Known antioxidant, methyl ester of sinapic acid (MESA) can interact with serum albumins.     

Vitamin B1-catalyzed aerobic oxidative esterification of aromatic aldehydes with alcohols

A straightforward aerobic oxidative esterification of aryl aldehydes with alcohols has been developed for the synthesis of substituted esters by employing vitamin B1 as a cost-effective, metal-free, and eco-friendly NHC catalyst. Air is used as a green terminal oxidant. The reaction is a useful addition to the existing NHC-catalytic oxidative esterification.

An aerobic oxidative esterification of aryl aldehydes with alcohols has been developed by employing vitamin B1 as a cost-effective, metal-free, and eco-friendly NHC catalyst.     

Cobalt(ii)-catalyzed benzylic oxidations with potassium persulfate in TFA/TFAA

A cobalt-catalyzed C(sp³)–H oxygenation reaction to furnish aldehyde was herein reported. This transformation demonstrated high chemo-selectivity, and tolerated various methylarenes bearing electron-withdrawing substituents. This reaction provided rapid access to diverse aldehydes form methylarenes. Notably, TFA/TFAA was used for the first time as a mixed solvent in cobalt-catalyzed oxygenation of benzylic methylenes.

A Co-catalyzed C(sp³)–H oxygenation reaction to furnish diverse aldehydes from methylarenes in TFA/TFAA is reported. This transformation demonstrated high chemo-selectivity, and tolerated with various methylarenes bearing electron-withdrawing substituents.     

Linear β-amino alcohol catalyst anchored on functionalized magnetite nanoparticles for enantioselective addition of dialkylzinc to aromatic aldehydes

A linear β-amino alcohol ligand, previously found to be a very efficient catalyst for enantioselective addition of dialkylzinc to aromatic aldehydes, has been anchored on differently functionalized superparamagnetic core–shell magnetite–silica nanoparticles (1a and 1b). Its catalytic activity in the addition of dialkylzinc to aldehydes has been evaluated, leading to promising results, especially in the case of 1b for which the recovery by simple magnetic decantation and reuse was successfully verified.

The catalytic activity of a linear β-amino alcohol ligand anchored on functionalized magnetite/silica core–shell nanoparticles has been evaluated in the addition of dialkylzinc to aldehydes leading to promising results.     

MOF-Zn-NHC as an efficient N-heterocyclic carbene catalyst for aerobic oxidation of aldehydes to their corresponding carboxylic acids via a cooperative geminal anomeric based oxidation

As an efficient heterogenous N-heterocyclic carbene (NHC) catalyst, MOF-Zn-NHC was used in the aerobic oxidation of aryl aldehydes to their corresponding carbocyclic acids via an anomeric based oxidation. Features such as mild reaction conditions and no need for a co-catalyst or oxidative reagent can be considered as the major advantages of the presented method in this study.

As an efficient heterogenous N-heterocyclic carbene (NHC) catalyst, MOF-Zn-NHC was used in the aerobic oxidation of aryl aldehydes to their corresponding carbocyclic acids via an anomeric based oxidation.     

Characterization of the volatile organic compounds produced from green coffee in different years by gas chromatography ion mobility spectrometry

The effect of storage time on green coffee volatile organic compounds (VOCs) was studied by their separation via head space solid-phase microextraction and identification via gas chromatography-ion mobility spectrometry. In total, 38 kinds of VOCs, mainly composed of alcohols, aldehydes, esters and ketones, were identified. The fingerprint showed that the VOCs produced by green coffee in different years had obvious differences, especially, acrolein, 3-methylbutyl acetate, butanoic acid, heptan-3-ol, and so on, that could be used to predict the storage time. In addition, with the increase of storage time, the contents of butanal, ethanol, dimethyl sulfide, propanal, butan-2-one had no obvious change, and could be considered as typical aroma characteristics of green coffee or special aroma components for variety identification. Meanwhile, principal component analysis (PCA) and “nearest neighbor” fingerprint analysis could also effectively distinguish green coffee with different storage times. Comprehensive analysis showed that GC-IMS technology could provide strong and favorable support for coffee storage.

The effect of storage time on green coffee VOCs was studied by their separation via HS-SPME and identification via GC-MS.     

N-Alkylation/aldol reaction of α-aldimino thioesters: a facile three-component coupling reaction

Theoretical calculation of the reactivity of α-imino thioesters indicates that they are very reactive substrates for Umpolung N-alkylation. In fact, treatment of α-aldimino thioesters with dialkylzinc reagents in the presence of aldehydes or imines gives three-component coupling products in good yields.

Treatment of α-aldimino thioesters with dialkylzinc reagents in the presence of aldehydes or imines gives three-component coupling products in good yields with good to high anti-selectivities.     

Enhancing the photo-efficacy of an organic visible-light-activated chromophore (alizarin red S) on zinc oxide with a Ag–Na electrolyte to photo-transform aromatic and aliphatic alcohols

The development of an aqueous silver-sodium/alizarin red sensitised zinc oxide system has been reported to oxidise a range of both aromatic and aliphatic alcohols to aldehydes. Furthermore, photoluminescence spectroscopy validated the electron quenching effect of zinc oxide''s defect sites after surface sensitising the metal-oxide with alizarin red. Powder diffuse reflectance UV/Vis data further substantiated the visible-light attenuated properties of alizarin red sensitised zinc oxide, and hence justification for its visible light reactivity towards alcohol oxidations. Lastly, density functional theory calculations supported the intermolecular photo-electronic transfer between alizarin red organic and zinc oxide.

An in-depth analysis into a dye-sensitised metal oxide system through photo-mechanical studies has extended the knowledge basis of semiconductor-mediated photocatalysis.     

Aldehyde catalysis – from simple aldehydes to artificial enzymes

Chemists have been learning and mimicking enzymatic catalysis in various aspects of organic synthesis. One of the major goals is to develop versatile catalysts that inherit the high catalytic efficiency of enzymatic processes, while being effective for a broad scope of substrates. In this field, the study of aldehyde catalysts has achieved significant progress. This review summarizes the application of aldehydes as sustainable and effective catalysts in different reactions. The fields, in which the aldehydes successfully mimic enzymatic systems, include light energy absorption/transfer, intramolecularity introduction through tether formation, metal binding for activation/orientation and substrate activation via aldimine formation. Enantioselective aldehyde catalysis has been achieved with the development of chiral aldehyde catalysts. Direct simplification of aldehyde-dependent enzymes has also been investigated for the synthesis of noncanonical chiral amino acids. Further development in aldehyde catalysis is expected, which might also promote exploration in fields related to prebiotic chemistry, early enzyme evolution, etc.

An overview of bio-inspired aldehyde catalysis is presented. High and sustainable catalytic activities of aldehydes are shown in different reactions.     

A doping-adsorption-pyrolysis strategy for constructing atomically dispersed cobalt sites anchored on a N-doped carbon framework as an efficient bifunctional electrocatalyst for hydrogen evolution and oxygen reduction

Renewable energy technology development focuses on the exploration of economical and efficient non-precious metal catalysts to replace precious metal catalysts in electrocatalytic reactions including oxygen reduction (ORR) and hydrogen evolution (HER). Herein, we synthesized a cobalt single atom catalyst anchored on a N-doped carbon framework by a doping-adsorption-pyrolysis strategy. The optimized Co SAs/CN-3 catalyst showed excellent HER and ORR bifunctional electrocatalytic performance, which could be attributed to the highly dispersed Co–N₄ active sites, large specific surface area and abundant pore structure. Density functional theory shows that the isolated active Co–N₄ site shows low hydrogen adsorption Gibbs free energy, and promotes the adsorption of H and oxygen-containing intermediates in HER and ORR. This work not only provides a new idea for the construction of transition metal catalysts with atomic accuracy but also provides powerful guidance for the development of efficient bifunctional electrocatalysts.

Atomically dispersed Co–N₄ sites anchored on a N-doped carbon framework catalyst were constructed by a novel doping-adsorption-pyrolysis strategy for bifunctional electrocatalytic HER and ORR.     

An iodine/DMSO-catalyzed sequential one-pot approach to 2,4,5-trisubstituted-1H-imidazoles from α-methylene ketones

A sequential one-pot approach to 2,4,5-trisubstituted imidazoles has been developed from α-methylene ketones and aldehydes. This methodology employs air-moisture stable reaction conditions and an inexpensive iodine/DMSO system affording a diverse range of known and novel (substrate scope) 2,4,5-trisubstituted imidazoles in moderate to excellent yields. The iodine/DMSO system was extended to the domino convergent synthesis of two functionalized intermediates, benzil and benzaldehyde, to produce the final product.

A sequential one-pot approach to 2,4,5-trisubstituted imidazoles has been developed from α-methylene ketones and aldehydes.     

Iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes

The first iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes was achieved. The reaction tolerates a wide range of functionalities. Furthermore, this protocol was found to be applicable to the oxidative transformation of allylic acetates. The proposed mechanism involves an oxygen transfer from solvent water to the carbonyl products.

The first iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes was effectively achieved.     

A solid-supported organocatalyst for asymmetric Mannich reaction to construct C2-quaternary indolin-3-ones

A simple and novel solid-supported organocatalyst from a 2-chlorotrityl chloride resin-immobilized 4-hydroxyproline was developed, and this organocatalyst has been used for the asymmetric Mannich reaction of 2-aryl-3H-indol-3-ones and aldehydes/ketones. A series of C2-quaternary indolin-3-ones were prepared in good yields (up to 83%) and with excellent diastereoselectivities (up to 20 : 1) and enantioselectivities (up to 99% ee). In addition, the organocatalyst can be recovered by simple filtration and also be reused for the asymmetric Mannich reaction without significant loss of catalytic efficiency.

A simple and novel solid-supported organocatalyst from a 2-chlorotrityl chloride resin-immobilized 4-hydroxyproline was developed, which has been used for the asymmetric Mannich reaction of 2-aryl-3H-indol-3-ones and aldehydes/ketones.     

Urazolium diacetate as a new,efficient and reusable Brønsted acid ionic liquid for the synthesis of novel derivatives of thiazolidine-4-ones

Urazolium diacetate catalyzed synthesis of new derivatives of 1,3-thiazolidine-4-ones (azo dispersive dyes family) via multicomponent reaction of various aldehydes, thioglycolic acid and 4-aminoazobenzene under solvent-free reaction was reported. This avenue for the synthesis of new derivatives of thiazolidine-4-one has advantages as: short reaction times, high yields, green aspect of chemistry and environmental friendliness, easy workup, solvent-free conditions and convenient operation.

Urazolium diacetate catalyzed synthesis of new derivatives of 1,3-thiazolidine-4-ones (azo dispersive dyes family) via multicomponent reaction of various aldehydes, thioglycolic acid and 4-aminoazobenzene under solvent-free reaction was reported.