Aryl Methyl Research Articles

T-BuOK-promoted methylthiolation of aryl fluorides with dimethyldisulfide under transition-metal-free and mild conditions

In the presence of potassium tert-butoxide (t-BuOK), the cross-coupling reaction between aryl fluorides and dimethyldisulfide was developed. A series of aryl methyl sulfides were obtained in moderate to good yields under transition-metal-free and mild conditions.

2-Aminoisoindoline-1,3-Dione-Functionalized Fe3O4/Chloro-Silane Core-Shell Nanoparticles as Reusable Catalyst: An Efficient Heterogeneous Magnetic Nanoparticles for Synthesis of 4H-Pyran Derivatives through Multicomponent Reaction

2-Aminoisoindoline-1,3-dione functionalized by Fe3O4@chloro-silane core-shell nanoparticles, then a green and convenient approach for the synthesis of a series of 4H-pyrans by the reaction of aryl aldehydes, malononitrile and methyl acetoacetate in ethanol/60 °C under by using magnetic nanoparticles (MNPs) of Fe3O4@SiO2-NH-isoindoline-1,3-dione is described. The characterization was performed by using a variety of conventional analytical instruments such as Fourier transform infrared spectra, field emission scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometer, thermal analysis. This method provides several advantages such as environmental friendliness, shorter time, excellent yields, easy separation of MNPs with using of external magnet and simple work-up procedure.

Convenient synthesis of 4,5-unsubstituted 3-aroylisoxazoles from methyl aryl ketones and (vinylsulfonyl)benzene in water

A convenient synthesis of 3-aroylisoxazoles from methyl ketones and (vinylsulfonyl)benzene in 2%TPGS-750-M/H2O has been developed. This reaction proceeds via tandem tert-butyl nitrite-promoted Csp3-H functionalization of methyl ketones, 1,3-dipolar cycloaddition and base-catalyzed aromatization, providing the corresponding products in moderate to good yields.

Molecular iodine mediated oxidative cleavage of the C–N bond of aryl and heteroaryl (dimethylamino)methyl groups into aldehydes

An efficient iodine mediated conversion of aryl or heteroaryl (dimethylamino)methyl compunds to aryl or heteroaryl aldehydes is achieved via cleavage of C-N bond.

QSAR studies on indole-azole Analogues using DTC tools; imidazole ring is more favorable for aromatase inhibition

Quantitative structure activity relationship (QSAR) studies have been performed on indole-azole based compounds to correlate molecular descriptors and aromatase inhibitory activity using Drug Theoretics and Cheminformatics (DTC) tools. For 2- and 3- [(aryl) (azolyl)methyl]indole derivatives (set-I), MATS4s, AATS4e, and ATSC7i showed good correlation with significant R2 and Q2 values as 0.93 and 0.83, while for 1-aryl-2-[(1H-imidazol-1-yl)methyl]-6-substituted-1H-indole derivatives (set-II), the derived QSAR model showed significant R2 and Q2 values as 0.93 and 0.82 respectively, with the descriptors AVP-0, MATS7s, minHaaCH. Electronic parameters such as high electronegativity and ionization potential have unfavourable influence on anti-aromatase activity of both series of compounds. Among the imidazole and 1, 2, 4-triazole rings, imidazole nucleus is more favourable due to its low electrostatic potential. The findings of the study might guide in future designing and development of more potent indole-azole based aromatase inhibitors.

1,5-Diketone derivatives in the synthesis of 2,6-diaryl-4-(pyridin-4-yl)pyridines

New 1,5-diaryl-3-(pyridin-4′-yl)pentane-1,5-diones were synthesized via the tandem reaction of pyridin-4-carbaldehyde with methyl (aryl) ketones in the presence of sodium hydride. The treatment of the diketones with ammonium acetate resulted in heterocyclization to 2,6-diaryl-4-(pyridin-4′-yl)pyridines.

An efficient method to prepare aryl acetates by the carbonylation of aryl methyl ethers or phenols

A low pressure of CO was used to prepare aryl acetates directly.

Nickel-catalyzed enantioselective vinylation of aryl 2-azaallyl anions.

A unique enantioselective nickel-catalyzed vinylation of 2-azaallyl anions is advanced for the first time. This method affords diverse vinyl aryl methyl amines with high enantioselectivities, which are frequently occurring scaffolds in natural products and medications. This C–H functionalization method can also be extended to the synthesis of enantioenriched 1,3-diamine derivatives by employing suitably elaborated vinyl bromides. Key to the success of this process is the identification of a Ni/chiraphos catalyst system and a less reducing 2-azaallyl anion, all of which favor an anionic vinylation route over a background radical reaction. A telescoped gram scale synthesis and a product derivatization study confirmed the scalability and synthetic potential of this method.

Reactions involving aryl methyl ketone and molecular iodine: a powerful tool in the one-pot synthesis of heterocycles

The preparation of heterocyclic compounds has attracted great attention in organic chemistry because of their extensive application in the field of bioactive molecules, materials science, and natural products.

Alumination of aryl methyl ethers: switching between sp2 and sp3 C-O bond functionalisation with Pd-catalysis.

The reaction of [{(ArNCMe)2CH}Al] (Ar = 2,6-di-iso-propylphenyl) with aryl methyl ethers proceeded with alumination of the sp3 C–O bond. The selectivity of this reaction could be switched by inclusion of a catalyst. In the presence of [Pd(PCy3)2], chemoselective sp2 C–O bond functionalisation was observed. Kinetic isotope experiments and DFT calculations support a catalytic pathway involving the ligand-assisted oxidative addition of the sp2 C–O bond to a Pd–Al intermetallic complex.

Selenocyanation of Aryl and Styryl Methyl Ketones in the Presence of Selenium Dioxide and Malononitrile: An Approach for the Synthesis of α-Carbonyl Selenocyanates.

A convenient method has been developed for the synthesis of α-carbonyl selenocyanates from aryl methyl ketones/styryl methyl ketones using selenium dioxide as the selenating agent under simple reaction conditions. This reaction has notable advantages over the traditional methods in terms of accessibility and affordability of the starting materials. The method features the interaction of aryl methyl ketones/styryl methyl ketones with selenium dioxide and malononitrile to afford a series of α-carbonyl selenocyanates in moderate to good yields.

Синтез и гетероциклизация 4-гидрокси-3-((2-гидрокси-4,4- диметил6-оксоциклогекс-1-ен-1-ил)(арил)метил)- 2H-хромен-2-онов

The possibility of obtaining asymmetric 1,5-diketones based on 4-hydroxy-2H-chromen-2-one and dimedone by three-component condensation in the presence of L-proline as a catalyst is shown. As a result, a series of 4-hydroxy3 - ((2-hydroxy-4,4-dimethyl-6-oxocyclohex1-en-1-yl) (aryl) methyl) -2H-chromen-2-ones was obtained with a yield of 25 up to 73%. The study revealed that the highest yield was observed for compounds containing fragments of ortho-substituted aldehydes capable of forming a hydrogen bond. For meta- and para-substituted – the lowest yield was observed. In the case of ortho-substitution this can be probably explained due to the stabilization of the intermediate complex by two intramolecular hydrogen bonds, which makes it possible to selectively obtain only one final product – 4-hydroxy-3 -((2-hydroxy4,4-dimethyl-6-oxocyclohex-1- en-1-yl) (aryl) methyl) -2Hchromen-2-one. The structure of the obtained products was confirmed by 1 H, 13C NMR, HSQC, HMBC spectroscopy. Considering the 1,5-diketone fragment for the above-described compounds, the possibility of their O-heterocyclization by propionic anhydride was suggested. Boiling 4-hydroxy-3 - ((2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl) (aryl) methyl) -2Hchromen-2-ones in anhydride medium for an hour resulted in obtaining a series of 7- (aryl) -10,10-dimethyl-7,9,10,11-tetrahydro-6H, 8H-chromeno [4,3-b] chromene-6,8-diones. Their structure was also confirmed by 1 H, 13C NMR, HSQC, HMBC spectroscopy.

Directing Group-Promoted Inert C-O Bond Activation Using Versatile Boronic Acid as a Coupling Agent.

A simple Ni(cod)2 and carbene mediated strategy facilitates the efficient catalytic cross-coupling of methoxyarenes with a variety of organoboron reagents. Directing groups facilitate the activation of inert C-O bonds in under-utilized aryl methyl ethers enabling their adaptation for C-C cross-coupling reactions as less toxic surrogates to the ubiquitous haloarenes. The method reported enables C-C cross-coupling with readily available and economical arylboronic acid reagents, which is unprecedented, and compares well with other organoboron reagents with similarly high reactivity. Extension to directing group assisted chemo-selective C-O bond cleavage, and further application towards the synthesis of novel bifunctionalized biaryls is reported. Key to the success of this protocol is the use of directing groups proximal to the reaction center to facilitate the activation of the inert C-OMe bond.

Gut Metabolism of Furanocoumarins: Proposed Function of Co O-Methyltransferase.

Gut metabolism of natural products is of great interest due to the altered biological activity of the metabolites. To study the gut metabolism of the dietary furanocoumarins, the biotransformation of Angelica dahurica was studied with human gut microbiota. The major components of Avenula dahurica, including xanthotoxin (1), bergapten (2), imperatorin (3), isoimperatorin (4), oxypeucedanin (5), and byakangelicol (6), were all metabolized by the human fecal sample, and each furanocoumarin was also biotransformed by Blautia sp. MRG-PMF1 responsible for intestinal O-demethylation. Oxypeucedanin (5) and byakangelicol (6) were converted to oxypeucedanin hydrate (9) and desmethylbyakangelicin (12), respectively. The gut microbial conversion of xanthotoxin (1) and bergapten (2) with the MRG-PMF1 strain resulted in the production of xanthotoxol (7) and bergaptol (8), respectively, due to the methyl aryl ether cleavage by O-methyltransferase. Unexpectedly, the biotransformation of prenylated furanocoumarins, imperatorin (3), and isoimperatorin (4) resulted in the corresponding deprenylated furanocoumarins of xanthotoxol (7) and bergaptol (8), respectively. The cleavage of the prenyl aryl ether group by gut microbiota was unprecedented metabolism. Our data presented the first deprenylation of prenylated natural products, presumably by the anaerobic prenyl aryl ether cleavage reaction catalyzed by Co-corrinoid enzyme.

Novel synthesis of 2‐Aminothiazoles via Fe(III)‐Iodine‐catalyzed Hantzsch‐type condensation

AbstractA novel iron‐iodine catalyzed one pot synthesis of 2‐aminothiazoles from methyl aryl ketones and thiourea is demonstrated. This protocol can be considered as a catalyzed version of the classical Hantzsch aminothiazole synthesis as it enables the in situ generation of α‐iodoketones in the reaction medium using catalytic amount of iodine leading to Hantzsch condensation with thiourea. The supply of iodine for multiple catalytic cycles is ensured by using catalytic amounts of iron as it enables iodide to iodine oxidation. The generality of this protocol is also well established in this manuscript by synthesizing a variety of 2‐aminothiazoles from different ketones and thiourea.

Total synthesis of (+)-diospongin A

Enantioselective total synthesis of 2,4,6-trisubstituted pyran natural product diospongin A is accomplished from benzaldehyde in 5 steps. Key reaction in the synthesis is the addition of a silyl enol ether derived from vinylogous aryl methyl ketone to chiral β-alkoxy aldehyde and subsequent oxa -Michael addition. • Short one-pot reaction conditions for the synthesis of diospongin A. • Involves the vinylogous Mukaiyama Aldol reaction, Silyl deprotection and Oxa-Michael reaction in one-pot. • 25% overall yield from benzaldehyde.

Trifluoroacetic Anhydride as an Activator in the Acylation of Aryl Methyl Ketones with Carboxylic Acids

Trifluoroacetic anhydride was used as an efficient activator of the acylation of aryl methyl ketones with carboxylic acids in the presence of Bronsted and Lewis acids (SF3SO3H, MeSO3H, 4-MeC6H4SO3H·H2O, BF3·Et2O). In all cases, the products were the corresponding β-diketones. In the reactions in the presence of boron trifluoride–diethyl ether complex, the products were isolated as BF2-chelates with high yields.

A novel DMSO-assisted regioselective iodination of aniline analogues

A metal- and oxidant-free electrophilic iodination of aniline analogues was achieved in high to excellent yields at room temperature in MTBE with 0 or 3.5 equivalents of DMSO. Examined substituents include N-alkyl, N,N-dialkyl, N-morpholinyl and N-piperazinyl as well as methyl, Br, CN and CO2CH3 aryl ring substitutions.

A simple and efficient route to 2‐arylimidazo[1,2‐a]pyridines and zolimidine using automated grindstone chemistry

AbstractA green and efficient mechanochemical method for the synthesis of a series of 2‐arylimidazo[1,2‐a]pyridines was developed using an electrical grinder. I2 catalyzed mechanochemical grinding facilitates the cyclocondensation reaction between various aryl methyl ketones and 2‐aminopyridines to afford 2‐arylimidazo[1,2‐a]pyridines in good yields at ambient temperature. The method was successfully used for the gram‐scale synthesis of a marketed drug, zolimidine. The noticeable advantages of this environmentally sustainable protocol include mild conditions, simple instrumentation, inexpensive catalyst, atom economy, short reaction time etc.

Transition metal free α-C-alkylation of ketones using secondary alcohols

A base-mediated α- C -alkylation of ketones with secondary alcohols has been developed. This transition metal free approach employs KO t -Bu as the base and exhibits a broad scope, allowing a range of commodity aliphatic secondary alcohols and 1-arylethanols to be employed as alkylating agents. Aryl methyl ketones undergo selective mono-α -C -alkylation in high isolated yields (23 examples, 65% average yield).