Broad Scope Research Articles

C(sp3)-H Carbonylative Cyclization of Hydrazones with CO2: Synthesis of Pyrazolone Derivatives.

A novel method is reported to synthesize various pyrazolones through transition-metal-free and redox-neutral 1°, 2°, or 3° C(sp3)-H carbonylative cyclization using 1 atm of CO2 as a green carbonyl source, featuring good functional group tolerance, a broad substrate scope, facile scalability, and easy product transformation. The utility of this method could be demonstrated by the applications in preparing useful synthetic intermediates and bioactive compounds.

Oxyphosphorodithiolation of Vinyl Azides with P4S10 and Alcohols Leading to β-Keto Phosphorodithioates.

A simple strategy for the synthesis of β-keto phosphorodithioates has been developed through the direct oxyphosphorodithiolation of vinyl azides with P4S10 and alcohols in the presence of water. The reaction is conducted at room temperature to provide a number of β-keto phosphorodithioates in moderate to good yields. This methodology has the advantages of simple operation, mild condition, broad substrate scope, and favorable group compatibility.

Rhodium-Catalyzed Synthesis of Trifluoromethyl-Containing Allylic Alcohols Via Z-Alkenyl Transfer with High Stereochemistry Retention.

Herein, we report the rhodium-catalyzed Z-alkenyl transfer from tertiary allylic alcohols to aryl trifluoromethyl ketones, which provided an efficient way of preparation of trifluoromethyl-containing Z-allylic alcohols via β-Z-alkenyl elimination. The key Z-alkenyl-rhodium species were generated with a high degree of stereochemical retention. This reaction featured a broad substrate scope and good functional tolerance and would offer a fascinating approach for the synthesis of Z-alkenes.

Modular Access to C2’‐Aryl/Alkenyl Nucleosides with Electrochemical Stereoselective Cross‐Coupling

AbstractChemically modified oligonucleotides have garnered significant attention in medicinal chemistry, chemical biology, and synthetic biology due to their enhanced stability in vivo compared to naturally occurring oligonucleotides. However, current methods for synthesizing modified nucleosides, particularly at the C2’‐position, are limited in terms of efficiency, modularity, and selectivity. Herein, we report a new approach for the synthesis of highly functionalized C2’‐α‐aryl/alkenyl nucleosides via an electrochemical nickel‐catalyzed cross‐coupling of 2’‐bromo nucleosides with a variety of (hetero)aryl and alkenyl iodides. This method affords a diverse array of C2’‐ α‐aryl/alkenyl nucleosides with excellent stereoselectivity, broad substrate scope, and good functional group compatibility. We further synthesized oligonucleotides incorporating C2’‐aryl‐modified thymidine moieties and demonstrated that their annealed double‐stranded DNAs exhibit decreased melting temperatures (Tm). Additionally, oligonucleotides with C2’‐aryl modifications at the 3’ end showed enhanced resistance to 3’‐exonuclease degradation and C2’‐aryl modifications did not impede the cellular uptake process, highlighting the potential of these modified oligonucleotides for therapeutic applications.

Nickel-Catalyzed Three-Component 1,1-Difunctionalization of Unactivated Alkenes with Quinoxaline/Naphthoquinone and Arylboronic Acids via Organometallic-Radical Relay.

A nickel-catalyzed intermolecular three-component 1,1-difunctionalization of unactivated alkenes with quinoxaline/naphthoquinone and arylboronic acids via organometallic-radical relay is developed. This efficient protocol provides a new method to access a variety of arylalkanes in moderate to good yields with a broad substrate scope and excellent functional group tolerance. The mechanistic studies provide insights into the mechanism and origin of chemo- and regioselectivity as well as confirm the generation of functionalized benzylic radicals.

Isu Kontemporer dalam Kajian Sosiolinguistik: Bahasa dan Gender

In interacting and communicating, the use of language plays a very important role. However, there are still many who experience misunderstandings in communicating in everyday life. This is due to the very broad scope of language meaning, as well as differences in language styles between individuals. There are various factors that influence this difference, such as environment, education level, gender, and so on. The purpose of this study is to identify a difference in language style between men and women. Based on the results of observations made by researchers, compared to men, women tend to look very expressive. In this study, it can be seen that there are differences in language between men and women. In terms of social position, it seems that men dominate women. Men have the freedom to speak directly, while women often do not. Men can interrupt conversations and use harsher language, while women are expected to maintain politeness and be gentle in speaking. This finding has significant implications for everyday social interactions. Differences in language styles for men and women can cause misunderstandings and tensions in interpersonal communication. In a broader context, this communication pattern reflects and reinforces gender inequality in society. This can impact power dynamics in the workplace, personal relationships, and participation in public spaces. Further research is needed to explore strategies that can bridge this communication gap and promote equality in verbal interactions between genders. Keywords: Sociolinguistics, Language, Gender

Highly Selective Hydrogenation of Nitriles to Primary Amines without an Additive Using Nanoscale Ni0-NiII/III-bTiO2 Heterojunctions.

Despite significant progress in the catalytic hydrogenation of nitriles, the persistent challenge of requiring additives to prevent condensation byproducts and achieve selectivity toward primary amines demands urgent attention. In this work, we present an integrated approach utilizing a ligand-bridged Ni-Ti bimetallic complex as a precursor to tune Ni0-NiO-NiO(OH) heterojunctions and phases of black titania (bTiO2) by controlling pyrolytic conditions. This tailored phase distribution and charge dynamics across heterojunctions create an effective balance of acidic and basic sites, enabling the direct hydrogenation of nitriles to primary amines without the need for additives. However, at elevated pyrolysis temperatures, this balanced composition begins to shift, with the loss of critical phases that alter the catalyst's structural and chemical properties. This shift reduces amphoteric behavior, resulting in decreased selectivity for primary amines and favoring the formation of condensation byproducts. The catalyst's structure, amphoteric nature, crystallinity, surface area, and active sites are comprehensively characterized using high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), temperature programmed desorption of ammonia (NH3-TPD), temperature programmed desorption of carbon dioxide (CO2-TPD), and CO2 adsorption techniques. The magnetically retrievable catalyst exhibited excellent functional group tolerance, high selectivity, multiple reusability, broad substrate scope, and high activity for nitrile hydrogenation to primary amines, with the potential for advanced catalytic hydrogenation of other functional groups.

Mengupas Sebuah Pendekatan Normatif dalam Mengembangkan Studi Islam

Basically, Islam is not merely a religion but also encompasses other components such as culture and knowledge that underlie it. As a religion, Islam has many dimensions that include faith, logic, economics, science and technology, environmental issues, history, and household life. Its broad scope allows Islam to embrace all differences that have become a reality of social and societal dynamics. It is not appropriate to interpret Islam using only one approach; instead, multiple approaches are necessary to allow Islam to permeate deeply and serve as a solution to every problem that arises in the realm of human life. Interpreting Islam normatively follows a deductive way of thinking, which starts from a belief that is considered true and certain, as all teachings originating from God are inherently true. Thus, they are not questioned but begin with belief, which is then reinforced by evidence and arguments.

One-Pot, Three-Component Coupling Synthesis of [(Benzothiazol-2-ylamino)(aryl)methyl]isoquinolinols under Catalyst- and Solvent-Free Conditions

AbstractA one-pot, three-component coupling procedure has been developed for the synthesis of [(benzothiazol-2-ylamino)(aryl)methyl]isoquinolinols via the reaction of hydroxyisoquinolines, aryl/heteroaryl/aliphatic aldehydes with 2-aminobenzothiazoles under catalyst- and solvent-free conditions. The developed 2′-aminobenzothiazolomethylation procedure is suitable to execute even on a gram scale and has a broad scope. The 2′-aminobenzothiazolomethylated products (Betti bases) were formed through the initial nucleophilic C-attack of hydroxyisoquinolines on aldehydes to generate the ortho-quinone methide (o-QM) as an intermediate, followed by 1,4-aza-Michael addition of 2-aminobenzothiazoles. Betti bases have significance in medicinal chemistry due to their wide range of pharmacological applications and they are useful ligands and catalysts in asymmetric synthesis.

Copper-Catalyzed Regio-, Diastereo-, and Enantioselective Allylic Alkylation with 1,1-Diborylalkanes.

We report a copper-catalyzed regio-, diastereo-, and enantioselective allylic alkylation of allyl bromides using 1,1-diborylalkanes as prochiral nucleophiles. This methodology employs copper(I) bromide as a catalyst, an (R)-BINOL-derived phosphoramidite as a ligand, and lithium benzoate as a crucial additive. The reaction affords enantioenriched homoallylic boronic esters possessing vicinal stereocenters in good yields and high diastereo- and enantioselectivity. The developed method demonstrates a broad substrate scope with respect to a wide range of 1,1-diborylalkanes and allyl bromides. Mechanistic studies, including deuterium-labeling experiments and DFT calculations, provide insights into the reaction pathway and the origin of the stereoselectivity. The synthetic utility of this method is showcased through various transformations of the obtained enantioenriched homoallylic boronic esters into valuable chiral building blocks.

Visible-Light-Induced Markovnikov Hydroalkoxylation of α-Trifluoromethyl Alkenes with ortho-Diketones.

We report, for the first time, a visible-light-promoted Markovnikov hydroalkoxylation of α-trifluoromethyl alkenes with 1,2-diketones. This transformation proceeded smoothly in the presence of a tertiary amine (Et3N), providing a series of enol ethers containing the trifluoromethylated tetrasubstituted center in moderate to excellent yields. In this protocol, hydrogen atom transfer between this amine and 1,2-diketone substrate affords a ketyl radical and an α-aminoalkyl radical, which engages in the formation of a radical anion of the α-CF3 alkene via a single electron transfer. Notably, this protocol features several advantages including metal- and external photocatalyst-free, mild conditions, easy operation, a broad substrate scope, and good functional group tolerance. Moreover, by applying this new method, a great number of important deuterium-labeled organofluorine compounds can be readily prepared using CD3OD as a deuterium source.

Iron-Catalyzed SO2-Retaining Smiles Rearrangement through Decarboxylation.

Radical Smiles rearrangements have emerged as powerful methodologies for constructing carbon-carbon bonds through intramolecular radical addition and fragmentation under milder conditions, with SO2 released as a byproduct. However, SO2-retaining Smiles rearrangements, which can yield valuable alkyl sulfone derivatives, have been scarcely explored. In this study, we present an unprecedented iron-catalyzed SO2-retaining Smiles rearrangement initiated by the decarboxylation of aliphatic carboxylic acids. This approach provides a mild, cost-effective, and versatile pathway to sulfone-containing compounds, demonstrating broad substrate scope and functional group tolerance. It offers a promising strategy for synthesizing γ- and δ-aryl substituted alkyl sulfones, which are traditionally challenging to produce.

Direct Reductive N‐alkylation of Amines with Carboxylic Esters

AbstractWe report herein a facile direct method for the reductive N‐alkylation of amines with carboxylic esters, using tert‐butylmagnesium chloride (t‐BuMgCl) as a mediator and Red‐Al as the reducing agent. The direct amidation of esters with amines and t‐BuMgCl generates the intermediate amides. Subsequently, without the need for isolation or purification, these intermediates reacted with Red‐Al in the same reaction flask to generate amines up to 90 % yield. This process is characterized by the rapid reaction time, quantitative conversion, and broad ester scope with various functional groups. Notably, this method enables the successful transformation of amine with carboxylic esters to produce cariprazine, a pivotal antipsychotic drug substance.

Co(III) or Ru(II)-Catalyzed Selective C-H Alkynylation of 2-Pyridones and Their Derivatives with Bromoalkynes.

We successfully reported selective C-H alkynylation of 2-pyridones with bromoalkynes under the catalysis of Co(III) or Ru(II). The alkynylation reaction used easily accessible bromoalkynes instead of high-valent iodine alkynes. There is a broad substrate scope of 2-pyridones with good yields. In addition, 2-pyridone can be used as a weakly directing group for C-H alkynylation of the proximal aryl C-H bond. This method offers an efficient approach for synthesizing diverse 2-pyridone derivatives, yielding alkynylated products up to 95% yield (>40 examples).

Palladium-Catalyzed Dual-Tasked ortho-C-H Borylation of Aryl Iodides.

The Pd-catalyzed ortho-C-H borylation of aryl iodides has been developed through maleimide-relayed C-H activation. In this reaction, the ipso-positions and ortho-C-H bonds of aryl iodides are alkylated and borylated, respectively, providing a new strategy for C-H borylation. The reaction exhibits a broad substrate scope and represents a modular synthetic method for functionalized 3-aryl succinimides, which are essential structural motifs in organic compounds with diverse biological activities. Furthermore, the boronate group can be further manipulated, and the practical utility of the reaction has been demonstrated. This work also introduces a new strategy for ipso, ortho-difunctionalization of aryl halides via C-H activation.

BINAP-Accelerated Copper-Mediated Photochemical Late-Stage Trifluoromethylation of Arenes.

Site-selective and late-stage C-H trifluoromethylation (including pentafluoroethylation) of arylthianthrenium salts using in situ generated CuCF3 from Ruppert-Prakash reagent under visible light was found to be significantly accelerated by a catalytic amount of rac-BINAP, allowing the reaction to complete within 15 min under very mild conditions without using any additional photoredox catalysts. The process showed a broad substrate scope, high efficiency, and excellent regioselectivity, which holds the promise to accelerate the discovery of fluorinated medicinal compounds.

Catalytic Asymmetric Synthesis of Inherently Chiral Eight‐Membered O‐Heterocycles through Cross‐[4+4] Cycloaddition of Quinone Methides

AbstractInherently chiral eight‐membered rings embedded in tetraphenylene derivatives and hetero‐analogues exhibit unique properties and allow diverse applications. A conceptually viable and straightforward approach to these frameworks is [4+4] cycloaddition, which still remains elusive. Herein, we describe the stereoselective cross‐[4+4] cycloaddition of quinone methides (QMs), leading to the formation of oxa‐analogues of tetraphenylene with exceptional chemo‐, diastereo‐, and enantioselectivity. The structures of these novel rigid eight‐membered O‐heterocycles were explored by single‐crystal X‐ray diffraction, and their stereochemical stability was elaborated through both density functional theory (DFT) calculations and thermal racemization experiments. The developed methodology exhibited broad substrate scope and the resulting cross‐[4+4] cycloadducts could be readily transformed into valuable chiral building blocks. Our findings expand the library of inherently chiral medium‐sized rings and also contribute to the advancement of asymmetric cross‐[4+4] cycloadditions of quinone methides.

Visible‐Light‐Mediated C−H Difluoroalkylation of (Hetero)arenes: A New Application of Vibration‐Induced‐Emission Molecule 9,14‐Diphenyl‐dihydrodibenzo[a,c]phenazine

AbstractHerein, we report a vibration‐induced emission molecule, 9,14‐diphenyl‐dihydrodibenzo[a,c]phenazines (DPAC), compound‐catalyzed C−H difluoroalkylation of (hetero)arenes under visible light conditions. This method demonstrates the promising potential of vibration‐induced‐emission (VIE) molecules in photocatalysis and facilitates a metal‐free synthetic approach for difluoroalkyl (hetero)arenes with broad substrate scope and functional group tolerance.

Base‐Mediated Sequential Annulation Reaction of Conjugated Dienes and Crotonate‐Derived Sulfur Ylides:Effective Synthesis of Bicyclo[4.1.0]heptenes

AbstractHerein we present a method for base‐mediated sequential annulation reaction of conjugated dienes. The method offers an efficient pathway for the effective construction of bicyclo[4.1.0]heptenes. Notable features of this approach include good yields, remarkable stereoselectivity, as well as a broad substrate scope and significant step efficiency. In addition, the reaction could be effectively scaled up to a gram scale under standard condition.

Synthesis of Functionalized Benzo[f]chromanes and Hydroxyalkyl Naphthols: Catalytic Coupling of Naphthols and Allylic Alcohols

AbstractCatalytic dearomatization of arenols is an uphill task that can serve as a powerful method to construct C−C bonds with unsaturated coupling partners. Herein, a simple and efficient strategy for coupling naphthols with allylic alcohols is reported. A single Ru(II) pincer catalyzed coupling of naphthols with primary allylic alcohols led to the formation of benzo(f)chromanes, whereas the use of secondary alcohols delivered the hydroxyalkyl naphthols. Broad substrate scope and good functional group tolerance are demonstrated. Notably, a high diastereoselectivity is attained on chromanes. Hydroxyalkyl naphthols are synthetically transformed into spiroethers, and dearomative bromination is achieved on chromanes. Mechanistic studies revealed the involvement of tandem reactions, a formal O−H bond activation of allylic alcohols by an active catalyst via amine‐amide metal‐ligand cooperation provided α‐β, unsaturated carbonyl intermediates, which further underwent 1,4 conjugate addition with dearomatized naphthols. One of the crucial intermediates, naphthyl radical, is elucidated by EPR studies and trapped using a radical scavenger. Liberated hydrogen and water molecules are the only byproducts in these transformations.