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Molecular platforms are essential components of various surface‐mounted molecular devices. Here, we document the synthesis of two universal triptycene‐based tripodal pedestals featuring terminal alkynes in the axial position. We showcase their versatility by incorporating them into the structures of diverse functional molecules such as unidirectional light‐driven molecular motors, photoswitches, and Brownian molecular rotors using standard cross‐coupling reactions. We also present their fundamental physical properties, including acidity constants, data from differential scanning calorimetry, and crystallographic analysis of two parent and five derived structures. Finally, and importantly, we demonstrate that the photochemical properties of selected photoswitch representatives remain uncompromised when fused with tripods. [ABSTRACT FROM AUTHOR]

Gold(III) complexes containing trifluoromethyl ligands are efficient catalysts in the hydration of alkynes, operating at low catalyst loadings, without additives, using environmentally friendly solvents and at mild conditions (60 °C). Hydration of terminal and internal alkynes provides the corresponding ketones in quantitative yields without special precautions as dry solvents or inert atmospheres. Remarkably, hydration of asymmetric internal alkynes proceeds with moderate to notable regioselectivities, providing mixtures of the two possible isomers with ratios up to 90 : 10. [ABSTRACT FROM AUTHOR]

A concise hydrosilylation of alkynes for synthesizing β‐(E)‐vinylsilanes catalyzed by dirhodium(II)/XantPhos has been developed. In this reaction, β‐(E)‐vinylsilanes were generated from the isomerization of β‐(Z)‐vinylsilanes catalyzed by dirhodium(II) hydride species rather than the direct insertion of triple bond into M−H or M−Si bond (traditional Chalk‐Harrod mechanism or modified Chalk‐Harrod mechanism). The hydrosilylation displayed a broad substrate scope for alkynes and tertiary silanes, tolerating diverse functional groups including halides, nitriles, amines, esters, and heterocycles. [ABSTRACT FROM AUTHOR]

Visible‐light‐mediated [2+2] photocycloaddition reaction can be considered an ideal solution due to its green and sustainable properties, and is one of the most efficient methods to synthesize four‐membered ring motifs. Although research on the [2+2] photocycloaddition of alkynes is challenging because of the diminished reactivity of alkynes, and the more significant ring strain of the products, remarkable achievements have been made in this field. In this article, we highlight the recent advances in visible‐light‐mediated [2+2] photocycloaddition reactions of alkynes, with focus on the reaction mechanism and the late‐stage synthetic applications. Advances in obtaining cyclobutenes, azetines, and oxetene active intermediates continue to be breakthroughs in this fascinating field of research. [ABSTRACT FROM AUTHOR]

Vinyl sulfones are crucial building blocks in synthetic chemistry and core structural units of pharmaceutically active molecules, thus extensive investigations have been conducted on the construction of these skeletons. In contrast to the classical synthetic approaches, the radical sulfonylation of alkynes for producing vinyl sulfones has garnered considerable interest because of its mild conditions and high efficiency. Radical sulfonation of alkynes typically begins with the sulfonyl radical attacking the alkynes, followed by further functionalization. Moreover, the association of metal‐catalyst‐free systems with multicomponent reactions (MCRs) offers an environmentally friendly pathway for efficiently constructing complex scaffolds from readily available partners. However, there is no comprehensive review summarizing the advancements in metal‐catalyst‐free multicomponent radical sulfonylation of alkynes. Hence, we provide a categorical overview based on the objects of sulfonylation of alkynes (hydrosulfonylation, carbosulfonylation, aminosulfonylation, oxysulfonylation, sulfosulfonylation, selenosulfonylation, and iodosulfonylation), along with interpretations of the reaction mechanisms. [ABSTRACT FROM AUTHOR]

Diarylacetylenes ArC≡CAr featuring condensed aromatic hydrocarbon fragments (Ar) such as naphthalene, anthracene, phenanthrene and pyrene were converted into vinylidene ligands by 1,2‐migration reactions within the coordination sphere of half‐sandwich complexes [MII(dppe)Cp]+ (MII = RuII, FeII). Comparison of the extent of conversion of the alkyne substrates to the vinylidene complexes [Ru{=C=CAr2}(dppe)Cp]+ with those obtained from acetylenes functionalized by smaller groups (H, CH3, Ph) show that the molecular volume (VM) of the migrating group and relief of steric congestion plays a role during the rearrangement process. Conversely, the H‐atoms from the larger condensed ring aryl groups that are in close proximity to the migrating sites also have a significant influence on the efficacy and extent of the reaction by restricting access of the alkyne to the metal center, resulting in a less effective migration reaction. This combination of competing steric factors (acceleration due to relief of steric congestion and restricted access of the alkyne moiety to the reaction site) is exemplified by the facile migration of 1‐pyryl entities and the low yields of vinylidene products formed from 1,2‐bis(9‐anthryl)acetylene. [ABSTRACT FROM AUTHOR]

The reaction between aldehydes or ketones and alkynes—the carbonyl‐alkyne metathesis—constitutes a very useful strategy for the synthesis of α,β‐unsaturated carbonyls. We now demonstrate that iodine is a highly efficient catalyst for both the intra‐ and intermolecular metathesis reaction in very small concentrations (0.1–1 mol %). Our protocol outperforms other catalytic systems, is operationally very simple, cheap, metal‐free, and tolerates a large variety of functional groups (e. g., −CN, −CO2Me, −Br, −OH) at very low catalyst loadings. We can furthermore show that iodine‐catalyzed carbonyl‐alkyne metatheses can be combined with other iodine‐catalyzed reactions in one‐pot procedures to afford larger and more complex molecular structures. Finally, our mechanistic studies indicate that the iodonium ion is the active catalyst under the reaction conditions. [ABSTRACT FROM AUTHOR]

In 1,1,1,3,3,3‐hexafluoroisopropyl alcohol (HFIP), gem‐bis(triflyl)cyclobutenes, which can be prepared by the (2+2) cycloaddition reaction of Tf2C=CH2 with alkynes, underwent desulfination to generate the corresponding cyclobutenyl cation. This unique reactivity was successfully applied to the Friedel–Crafts type cyclobutenylation reaction of several (hetero)aromatic compounds. [ABSTRACT FROM AUTHOR]

Green chemistry strives for sustainability at the molecular level and is gaining increasing relevance in the development of chemical reactions. The haloalkynylation reaction is a highly atom–economical C−C coupling reaction that was previously only achieved using transition metal catalysts. It enables the introduction of an alkyne unit and a halogen atom into the target molecule. Herein, we present a haloalkynylation reaction catalyzed by indium(III) halides. The use of indium(III) bromide as a catalyst leads exclusively to the cis addition products with yields up to 86 %. In addition, iodoacetylenes can be applied for the first time for the haloalkynylation reaction of internal alkynes which is an important step forward in the development of industrially relevant and sustainable catalysts. In contrast to gold catalysis, which proceeds via a similar mechanism, the use of alkyl‐substituted haloacetylenes as reagents is also possible. Based on 13C labeling experiments and quantum chemical calculations, we postulate two possible mechanisms for the indium(III)‐catalyzed haloalkynylation reactions. [ABSTRACT FROM AUTHOR]

14,14′‐Bidibenzo[a,j]anthracenes (BDBAs) were prepared by iridium‐catalyzed annulation of 5,5′‐biterphenylene with alkynes. The molecular geometries of overcrowded BDBAs were verified by X‐ray crystallography. The two dibenzo[a,j]anthryl moieties are connected through the sterically hindered 14 positions, resulting in highly distorted molecular halves. The conformation with a small twist angle between two molecular halves can minimize steric conflicts between the substituents at 1 and 13 positions and the carbon atoms of the central axis, as well as steric clashes between those substituents. One such example is octafluoro‐substituted BDBA, where the interplanar angle between two anthryl moieties is approximately 31° (currently the lowest reported value, cf. 81° in 9,9′‐bianthracene). The intramolecular interactions and electronic couplings between two molecular halves resulted in upfield 1H NMR signals, redshifted absorption and emission bands, and a reduced HOMO–LUMO gap. Photodynamic investigations on BDBAs indicated that the formation of the conventional symmetry‐breaking charge transfer (SBCT) state was suspended by restricted rocking around the central C−C bond. Such a mechanism associated with this highly constrained conformation was examined for the first time. [ABSTRACT FROM AUTHOR]

Nickel‐catalyzed intramolecular hydrosilylation can be efficiently achieved with high regio‐ and stereoselectivities through two distinct methodologies. The first approach utilizes a conventional method, involving the reduction of nickel salt (NiBr2‐2,2'‐bipyridine) using manganese metal. The second method employs a one‐step electrochemical reaction, utilizing the sacrificial anode process and NiBr2bipy catalysis. Both methods yield silylated heterocycles in good to high yields through a syn‐exo‐dig cyclization process. Control experiments and molecular electrochemistry (cyclic voltammetry) provided further insights into the reaction mechanism. [ABSTRACT FROM AUTHOR]

Utilizing periodic acid as an environmentally benign oxidizing agent, this study introduces a novel mechanochemical method that mimics ozonolysis to convert internal alkynes into 1,2‐diketones, showcasing effective emulation of ozone's reactivity. Notably, this oxidation occurs at room temperature in aerobic conditions, eliminating the need for toxic transition metals, hazardous oxidants, or expensive solvents. Through control experiments validating the mechanism, substantial evidence supports a concerted reaction pathway. This progress marks a significant stride toward cleaner and more efficient chemical synthesis, mitigating the environmental impact of conventional processes. Assessing the green chemistry metrics in both solvent‐free and previously reported solvent‐based methods, our eco‐friendly protocol demonstrates an E‐factor of 7.40, a 51.7 % atom economy, a 45.5 % atom efficiency, 100 % carbon efficiency, and 11.9 % reaction mass efficiency when solvents are not used. [ABSTRACT FROM AUTHOR]

Utilizing periodic acid as an environmentally benign oxidizing agent, this study introduces a novel mechanochemical method that mimics ozonolysis to convert internal alkynes into 1,2‐diketones, showcasing effective emulation of ozone's reactivity. Notably, this oxidation occurs at room temperature in aerobic conditions, eliminating the need for toxic transition metals, hazardous oxidants, or expensive solvents. Through control experiments validating the mechanism, substantial evidence supports a concerted reaction pathway. This progress marks a significant stride toward cleaner and more efficient chemical synthesis, mitigating the environmental impact of conventional processes. Assessing the green chemistry metrics in both solvent‐free and previously reported solvent‐based methods, our eco‐friendly protocol demonstrates an E‐factor of 7.40, a 51.7 % atom economy, a 45.5 % atom efficiency, 100 % carbon efficiency, and 11.9 % reaction mass efficiency when solvents are not used. [ABSTRACT FROM AUTHOR]

Ruthenium(II)‐catalyzed synthesis of π‐conjugated fused imidazo[1,5‐a]quinolin‐2‐ium derivatives have been achieved via C−H activation of quinoline‐functionalized NHC (NHC=N‐heterocyclic carbene) and oxidative coupling with internal alkynes. The reaction occurred with high efficiency, broad substrate scope, tolerates a wide range of functional groups and utilized into a gram‐scale. Synthetic applications of the coupled product have been exemplified in the late‐stage derivatization of various highly functionalized scaffolds. Moreover, most of the annulated products exhibit intense fluorescence and have potential applications in optoelectronic devices. Mechanistic studies have provided insights into the spectroscopic characterization of key five‐membered ruthenacycle intermediate and Ru(0) sandwich species. Based on several control experiments, deuterium‐kinetic isotope effect, and thermodynamic activation parameters the mechanistic finding demonstrated that fused imidazo‐[1,5‐a]quinolin‐2‐ium C(2)−H bond cleavage is the rate‐determining step and ruling out the possibility of reductive elimination for controlling the rate of reaction. [ABSTRACT FROM AUTHOR]

Catalytic cross‐coupling between aryl halides and alkynes is considered an extremely important organic transformation (popularly known as the Sonogashira coupling) and it requires a transition metal‐based catalyst. Accomplishing such transformation without any transition metal‐based catalyst in the absence of any external stimuli such as heat, photoexcitation or cathodic current is highly challenging. This work reports transition‐metal‐free cross‐coupling between aryl halides and alkynes synthesizing a rich library of internal alkynes without any external stimuli. A chemically double‐reduced phenalenyl (PLY)‐based molecule with the super‐reducing property was employed for single electron transfer to activate aryl halides generating reactive aryl radicals, which subsequently react with alkyne. This protocol covers not only various types of aryl, heteroaryl and polyaryl halides but also applies to a large variety of aromatic alkynes at room temperature. With a versatile substrate scope successfully tested on more than 75 entries, this radical‐mediated pathway has been explained by several control experiments. All the key reactive intermediates have been characterized with spectroscopic evidence. Detailed DFT calculations have been instrumental in portraying the mechanistic pathway. Furthermore, we have successfully extended this transition‐metal‐free catalytic strategy for the first time towards solvent‐free cross‐coupling between solid aryl halide and alkyne substrates. [ABSTRACT FROM AUTHOR]

A safe and efficient method for the in‐situ preparation of (diazomethyl)dimethylphosphine oxide – a hereto unexplored diazoalkane reagent – is developed. The method is based on the diazotization of the corresponding P(O)Me2‐substituted amine (readily available in multigram quantities) in non‐aqueous media. The protocol provides the target product as ca. 1.5 M CHCl3 solution which is stable at −18 °C. The utility of the synthesized diazoalkane is illustrated by its [3+2] cycloaddition with electron‐poor alkynes and alkenes providing the corresponding P(O)Me2‐substituted pyrazoles and pyrazolines with moderate to good efficiency. In this view, the title compound represents and an important extension of medicinally relevant phosphine oxide reagents. [ABSTRACT FROM AUTHOR]

We report an efficient iron-catalyzed cycloaddition procedure leading to the construction of (hetero)aromatic rings by alkyne [2+2+2] cycloisomerization. This method relies on the use of an air-stable (N,N)Fe(II) precursor easily prepared from a commercially available ligand derived from 1,10-phenanthroline, reduced in situ into a catalytically active non-innocent (N,N *-)2Fe(II) species. This system displays a large scope application, operates under mild conditions and at low catalytic charges (25 cycloadducts formed, up to 1.5 mol% catalyst). Moreover, this method also enables access to 29 cycloadducts by crosscycloisomerization between 1,6- or 1,7-diynes and alkynes in near-equimolar conditions. 1,3,5-Triazines can also be prepared with this procedure starting from the corresponding cyanamides. Scale-up reactions and post-functionalization of several cycloadducts also show that this [2+2+2] cycloaddition can be used in multistep sequences. [ABSTRACT FROM AUTHOR]

The particular and unique mechanism of the copper‐catalyzed reaction between azides and alkynes (CuAAC) has not only allowed for the efficient synthesis of 1,2,3‐trisubstituted 1,4‐triazoles in excellent yields and under mild conditions, becoming the quintessential click reaction, but it has also enabled the straightforward formation of a metallocycle intermediate, the copper triazolyl. This, under suitable reaction conditions able to suppress its protonolysis, can be used either for the creation of new bicyclic triazolyl structures or for the generation of novel three or four‐component reactions. The aim of this review is to rationalize and unify all these transformations, which are collectively referred to as "interrupted click reactions". [ABSTRACT FROM AUTHOR]

A convenient and versatile approach to important 1‐azaspirocyclic systems relevant to medicinal chemistry and natural products is reported herein. The main strategy relies on a reductive decarboxylative cyclization of redox‐active esters which can be rapidly assembled from abundant cyclic azaacids and tailored acceptor sidechains, with a focus on alkyne acceptors enabling the generation of useful exo‐alkene moieties. Diastereoconvergent variants were studied and could be achieved either through remote stereocontrol or conformational restriction in bicyclic carbamate substrates. Two sets of metal‐free photocatalytic conditions employing inexpensive eosin Y were disclosed and studied experimentally to highlight key mechanistic divergences. [ABSTRACT FROM AUTHOR]

The reactivity of sydnones and sydnonimines toward terminal alkynes under copper catalysis has been explored using High‐Throughput‐Experimentation. A large panel of ligands and reaction conditions have been tested to optimize the copper‐catalyzed sydnone click reaction discovered by our group ten years ago. This screening approach led to the identification of new ligands, which boosted the catalytic properties of copper and allowed the discovery of a new copper‐catalyzed click‐and‐release reaction involving sydnonimines. This reaction allowed chemoselective ligation of terminal alkynes with sydnonimines and, simultaneously, the release of an isocyanate fragment molecule that can be used for further transformations. [ABSTRACT FROM AUTHOR]

Although challenging, the distant C−H functionalization with precision is quite rewarding and has long been intriguing. Tailoring an appropriate template accomplishes the job but the prerequisite sets the limitation. We herein unveil our discovery of annulation of alkynes on to two distant (from directing group) C−H bonds through rollover cyclometallation assisted by conjugated C=C bond. The annulation follows a concomitant cyclization rewarding a rare triple C−H functionalization. The annulation is totally regioselective with an array of unsymmetrical alkynes, taking the leverage of an extended conjugation or a tertiary hydroxyl co‐ordination. The mechanism is supported by control experiments, KIE & labelling studies and Mass spectrometry. [ABSTRACT FROM AUTHOR]

This study shows the first example of cycloaddition–retro‐electrocyclization (CA‐RE) click reaction involving nitrogen end‐capped push‐pull oligoynes. The reported CA‐RE reaction with TCNE (tetracyanoethylene) is fully regioselective and leads exclusively to the unprecedented TCBD (tetracyanobuta‐1,3‐diene‐2,3‐diyl) end‐capped carbon rods. The molecular structure of the products was unambiguously confirmed using X‐ray single crystal diffraction and their optical and electronic properties were investigated experimentally and rationalized using DFT (density functional theory) calculations. [ABSTRACT FROM AUTHOR]

In the vibrant field of SF5 chemistry, SF5X reagents (X=F, Cl, Br) are at the heart of current investigations in radical pentafluorosulfanylation reactions. SF5I is the missing link whose existence has not been reported despite its potential as SF5 donor. This study reports the formal addition of the hitherto unknown SF5I reagent to alkynes by means of a combination of SF5Cl/KI/18‐crown‐6 ether. The exclusive regio‐ and stereoselective synthesis of unprecedented (E)‐1‐iodo‐2‐(pentafluoro‐λ6‐sulfanyl) alkenes was achieved. A consensus was reached through computational and mechanistic studies for the realistic formation of SF5− anion but not SF5I in solution and the rational involvement of SF5⋅ and iodine radicals in the iodo pentafluorosulfanylation reaction. [ABSTRACT FROM AUTHOR]

A metal‐free tunable 1,2‐difunctionalization of the terminal alkynes showcasing a tandem installation of C−C and C−S bonds has been developed. The key enabling factor for the approach is the use of acetic acid as an acyl source to synthesize β‐substituted α,β‐unsaturated ketones. The reaction at room temperature leads to the regioselective acylation at the terminal carbon of alkynes, whereas at −78 °C, the acylation occurs at the more substituted carbon. [ABSTRACT FROM AUTHOR]

The synthesis of phosphines with light controlled basicity is presented in this study. A methodological approach for the preparation of these unconventional photochromic phosphines based on a dithienylethene organic moiety is reported. It relies on the palladium‐catalyzed annulation of alkynyl phosphines in the presence of a 2,3‐Dithienylsilacyclopropene. Accordingly, a diphenyphosphino moiety is connected to the organic photochrome thanks to different linkers. Their influence on the photochromism and on the phosphinyl group basicity is studied and evaluated based on experimental an NMR descriptor as well as DFT calculations. [ABSTRACT FROM AUTHOR]

The addition of heteroatom compounds to alkynes and alkenes is an atom‐efficient method of carbon‐heteroatom bond formation and is widely used as a fundamental synthetic method for the construction of functional molecules. Nevertheless, examples of transition‐metal‐catalyzed addition reactions of group 16 heteroatom compounds to carbon‐carbon unsaturated bonds have been limited due to the widespread belief that organic sulfur and selenium compounds are representative catalyst poisons. In recent decades, however, several seminal catalytic reactions of sulfur compounds have been developed, providing important insights into catalysis and poisons. Therefore, this paper focuses on the transition‐metal‐catalyzed addition of organosulfur compounds to alkynes and alkenes, gains comprehensive insights into the catalysis and catalyst poisons, and proposes concepts for the development of transition‐metal‐catalyzed reactions of group 16 heteroatom compounds. [ABSTRACT FROM AUTHOR]

In this work, we have developed selective methods for the synthesis of quinoline‐2‐carboxylates and quinoline‐3‐carboxylates as well as (indolin‐2‐ylidene)acetates through copper‐, silver‐, or phosphine‐catalyzed reaction of propiolates with 2′‐amino‐2,2,2‐trifluoroacetophenones. The approaches proposed ensure synthesis of substituted quinoline carboxylates and (indolin‐2‐ylidene)acetates in good yields. Introduction of alkynones into the reaction with 2′‐amino‐2,2,2‐trifluoroacetophenones gives acyl substituted derivatives in good yields. [ABSTRACT FROM AUTHOR]

Recently, it was reported that the alkynyl modification of nucleobases mitigates the toxicity of antisense oligonucleotides (ASO) while maintaining the efficacy. However, the general effect of alkynyl modifications on the duplex‐forming ability of oligonucleotides (ONs) is unclear. In this study, post‐synthetic nucleobase modification by Sonogashira coupling in aqueous medium was carried out to efficiently evaluate the physiological properties of various ONs with alkynyl‐modified nucleobases. Although several undesired reactions, including nucleobase cyclization, were observed, various types of alkynyl‐modified ONs were successfully obtained via Sonogashira coupling of ONs containing iodinated nucleobases. Evaluation of the stability of the duplex formed by the synthesized alkynyl‐modified ONs showed that the alkynyl modification of pyrimidine was less tolerated than that of purine, although both the modifications occurred in the major groove of the duplex. These results can be attributed to the bond angle of the alkyne on the pyrimidine and the close proximity of the alkynyl substituents to the phosphodiester backbone. The synthetic method developed in this study may contribute to the screening of the optimal chemical modification of ASO because various alkynyl‐modified ONs that are effective in reducing the toxicity of ASO can be easily synthesized by this method. [ABSTRACT FROM AUTHOR]

We report a selectivity‐switchable nickel hydride‐catalyzed methodology that enables the stereocontrolled semi‐reduction of internal alkynes to E‐ or Z‐alkenes under very mild conditions. The proposed transfer semi‐hydrogenation process involves the use of a dual nickel/photoredox catalytic system and triethylamine, not only as a sacrificial reductant, but also as a source of hydrogen atoms. Mechanistic studies revealed a pathway involving photo‐induced generation of nickel hydride, syn‐hydronickelation of alkyne, and alkenylnickel isomerization as key steps. Remarkably, mechanistic experiments indicate that the control of the stereoselectivity is not ensuing from a post‐reduction alkene photoisomerization under our conditions. Instead, we demonstrate that the stereoselectivity of the reaction is dependent on the rate of a final protonolysis step which can be tuned by adjusting the pKa of an alcohol additive. [ABSTRACT FROM AUTHOR]

The hydrofluorination of alkynes is an efficient synthetic route to monofluoroalkenes or difluoroalkanes. Both fluorinated motifs have found applications in medicinal chemistry and beyond. This review explores the recent advances in the hydrofluorination of diverse alkynes through various activation methods, from classical coinage metal catalysis to metal‐free conditions. The range of alkynes goes from the simplest unactivated alkynes to activated ones (ynones and derivatives, ynamides, alkynyl sulfides and sulfones as much as haloalkynes). Regio‐ and stereoselective methods exists, but there is still room for improvement depending on the type of alkyne. [ABSTRACT FROM AUTHOR]

An efficient, simple and general protocol for the selective hydration of terminal alkynes into the corresponding methyl ketones has been developed by using a cheap, easy‐to‐synthesise and sustainable FeIII‐based eutectic mixture [FeCl3 ⋅ 6H2O/Gly (3 : 1)] as both promoter and solvent for the hydration reaction, working: i) under mild (45 °C) and bench‐type reaction conditions (air); and ii) in the absence of ligands, co‐catalysts, co‐solvents or toxic, non‐abundant and expensive noble transition metals (Au, Ru, Pd). When the final methyl ketones are solid/insoluble in the eutectic mixture, the hydration reaction takes place in 30 min, and the obtained methyl ketones can be isolated by simply decanting the liquid FeIII‐DES, allowing the direct isolation of the desired ketones without VOC solvents. By using this straightforward and simple isolation protocol, we have been able to recycle the FeIII‐based eutectic mixture system up to eight consecutive times. Furthermore, the FeIII‐eutectic mixture is able to promote the selective and efficient formal oxidation of internal alkynes into 1,2‐diketones, with the possibility of recycling this system up to three consecutive times. Preliminary investigations into a possible mechanism for the oxidation of the internal alkynes seem to indicate that it proceeds through the formation of the corresponding methyl ketones and α‐chloroketones. [ABSTRACT FROM AUTHOR]

Seven‐exo‐dig hydrocarboxylation of nonactivated internal alkynes with conformationally flexible linker chains was achieved with cooperative gold‐zinc catalysts composed of an imidazo[1,5‐a]pyridinylidene ligand including a bipyridine coordination site at the C5 position. A proximity effect of the gold and zinc sites was essential for their high catalytic activity, in which the internal alkyne activated by the cationic gold species was attacked by the carboxylic acid deprotonated by the basic zinc site. Using a gold(I)‐complex with a bulky aromatic N‐substituent, 2,6‐dibenzhydryl‐4‐methylphenyl group, for the NHC ligand facilitated seven‐membered ring formation while minimizing intermolecular hydrocarboxylation as an undesired side reaction. The reaction mechanism was investigated by quantum chemical calculations. [ABSTRACT FROM AUTHOR]

We report the development of Pd/Cu‐catalyzed selective 2,1‐borocarbonylation reactions of aliphatic terminal alkynes with aryldiazonium salts and B2Pin2 to prepare gem‐bis(boryl) ketones in one‐pot. A series of corresponding products are obtained with good to excellent yields under a carbon monoxide atmosphere (10 bar). In addition, wide functional‐group tolerance can be observed. Preliminary mechanistic studies reveal that ethyl acetate serves as a proton source in the reaction. [ABSTRACT FROM AUTHOR]

Despite their long history and their synthetic potential underlined by various recent advances, radical thiol‐yne coupling reactions have so far only rarely been exploited for the functionalization of biomolecules, and no examples yet exist for their application in live cells ‐ although natural thiols show widespread occurrence therein. By taking advantage of the particular cellular conditions of mitochondria in cancer cells, we have demonstrated that radical thiol‐yne coupling represents a powerful reaction principle for the selective targeting of these organelles. Within our studies, fluorescently labeled reactive alkyne probes were investigated, for which the fluorescent moiety was chosen to enable both mitochondria accumulation as well as highly sensitive detection. After preliminary studies under cell‐free conditions, the most promising alkyne‐dye conjugates were evaluated in various cellular experiments comprising analysis by flow cytometry and microscopy. All in all, these results pave the way for improved future therapeutic strategies relying on live‐cell compatibility and selectivity among cellular compartments. [ABSTRACT FROM AUTHOR]

Cyclopentadienyliron dicarbonyl‐based complexes present opportunities for underexplored disconnections in synthesis. Access to challenging dihydropyrrolone products is achieved by propargylic C−H functionalization of alkynes for the formation of cyclic organoiron species. Excellent regioselectivity for unsymmetrical alkynes is observed in many cases. Notably, regioselectivity under these stoichiometric conditions diverges from those observed previously under catalysis, occurring at the more‐substituted terminus of the alkyne, allowing for methine functionalization and the formation of quaternary centers. Divergent demetallation of the intermediate organoiron complexes gives access to chemically diverse products which are amenable to further functionalization. [ABSTRACT FROM AUTHOR]

Hydrosilylation of C=C double and C≡C triple bonds is one of the most widely used processes in organosilicon chemistry, mostly catalyzed by Pt‐based complexes. Herein, the synthesis of a dicationic Zn+2‐based complex with a tripodal tris(2‐pyridylmethyl)amine (TPA) ligand is reported which was found to be a highly chemoselective catalyst for hydrosilylation reactions of alkynes. Mechanistic studies revealed that unlike typical Zn‐catalyzed hydrosilylation reactions where the key step is the activation of the Si−H bond, this system catalyzes the hydrosilylation reaction through the activation of C≡C triple bonds, which presumably is the reason for its high chemoselectivity. Remarkably, the hydrosilylation of alkynes could be performed in the presence of alkenes and other functional groups that remained intact in this reaction. [ABSTRACT FROM AUTHOR]

Herein, the tandem synthesis of various CF3Se‐containing heterocyclic compounds has been developed, using Tf2O as the catalyst and trifluoromethyl selenoxides as the electrophilic trifluoromethylselenolation reagents. This process is characterized by its mild conditions, ease of operation, and good functional group compatibility. A variety of alkynes could be transferred into CF3Se‐containing indoles, benzofurans, benzothiophenes, isoquinolines and chromenes in good yields. A key step involving the formation of the electrophilic CF3Se species was proposed. [ABSTRACT FROM AUTHOR]

Small heteroaryl‐diyne (Het‐DY) tags with distinct vibrational frequencies, and physiologically relevant cLog P were designed for multiplexed bioorthogonal Raman imaging. Pd−Cu catalyzed coupling, combined with the use of Lei ligand, was shown to improve overall yields of the desired heterocoupled Het‐DY tags, minimizing the production of homocoupled side‐products. Spectral data were in agreement with the trends predicted by DFT calculations and systematic introduction of electron‐ rich/poor rings stretched the frequency limit of aryl‐capped diynes (2209–2243 cm−1). The improved Log P of these Het‐DY tags was evident from their diffuse distribution in cellular uptake studies and functionalizing tags with organelle markers allowed the acquisition of location‐specific biological images. LC–MS‐ and NMR‐based assays showed that some heteroaryl‐capped internal alkynes are potential nucleophile traps with structure‐dependent reactivity. These biocompatible Het‐DY tags, equipped with covalent reactivity, open up new avenues for Raman bioorthogonal imaging. [ABSTRACT FROM AUTHOR]

Exploiting bimetallic cooperation alkali‐metal manganate (II) complexes can efficiently promote oxidative homocoupling of terminal alkynes furnishing an array of conjugated 1,3‐diynes. The influence of the alkali‐metal on these C−C bond forming processes has been studied by preparing and structurally characterizing the alkali‐metal tetra(alkyl) manganates [(TMEDA)2Na2Mn(CH2SiMe3)4] and [(PMDETA)2K2Mn(CH2SiMe3)4]. Reactivity studies using phenylacetylene as a model substrate have revealed that for the homocoupling to take place initial metalation of the alkyne is required. In this regard, the lack of basicity of neutral Mn(CH2SiMe3)2 precludes the formation of the diyne. Contrastingly, the tetra(alkyl) alkali‐metal manganates behave as polybasic reagents, being able to easily deprotonate phenylacetylene yielding [{(THF)4Na2Mn(C≡CPh)4}∞] and [(THF)4Li2Mn(C≡CPh)4]. Controlled exposure of [{(THF)4Na2Mn(C≡CPh)4}∞] and [(THF)4Li2Mn(C≡CPh)4] to dry air confirmed their intermediary in formation of 1,4‐diphenyl‐1,3‐butadiyne in excellent yields. While the Na/Mn(II) partnership proved to be the most efficient in stoichiometric transformations, under catalytic regimes, the combination of MC≡CAr (M= Li, Na) and MnCl2 (6 mol %) only works for lithium, most likely due to the degradation of alkynylsodiums under the aerobic reaction conditions. [ABSTRACT FROM AUTHOR]

In photo‐induced olefin synthesis, the photocatalysts with high triplet energy could cause the isomerization of olefins. This study demonstrates a new quinoxalinone photocatalytic system for highly stereoselective alkenes preparation from alkenyl sulfones and alkyl boronic acids. Our photocatalyst could not convert the thermodynamically favored E‐olefin to Z‐olefin, guaranteeing the high E‐configuration selectivity of the reaction. There is weak interaction between boronic acids and quinoxalinone according to NMR experiments, probably decreasing the oxidation potential of boronic acids. This system can be further extended to the allyl and alkynyl sulfones to give corresponding alkenes and alkynes. [ABSTRACT FROM AUTHOR]

As the key intermediates in metal‐promoted/catalyzed C−C bond coupling reactions of nitriles and alkynes, azametallacyclopentadienes, M(N=CR1−CR2=CR3), are an important class of azametallacycles. Although the first authentic azametallacyclopentadienes were documented in 1986, their chemistry towards solid‐state structures, intrinsic reactivity, and synthetic application was rarely investigated for a long time. At the beginning of this century, seminal works about the applications of azametallacyclopentadienes in the synthesis of heterocycles, including multi‐substituted pyridines, isoquinolines, furans, and pyrroles were reported. Subsequently, a series of new complexes with this motif, namely the Group 4, aluminum, actinide, and rare‐earth azametallacyclopentadienes were isolated and structurally characterized. Among them, the rare‐earth azametallacyclopentadiene expresses high reactivity towards unsaturated molecules, such as nitriles, isocyanides, and Mo(CO)6 to provide novel fused metallacycles. In this Concept, we reviewed the advances in the preparation, reactivity, and synthetic application of azametallacyclopentadienes in the past twenty years. [ABSTRACT FROM AUTHOR]

Tetraarylethylenes (TAEs) have been gaining attention from various scientific disciplines for their characteristic chemical and physical properties. From the synthetic perspective, however, efficient methods for the selective synthesis of different isomers of TAEs are still underdeveloped. Here, we report the regio‐ and stereoselective synthesis of TAEs by means of sodium‐promoted reductive anti‐1,2‐dimagnesiation of alkynes. Subsequent transmetallation to zinc generates trans‐1,2‐dizincioalkenes, which underwent the stereoselective arylation under a palladium catalysis to afford a variety of TAEs that had been difficult to prepare according to the conventional procedures. In addition, the present method accommodates not only diarylacetylenes but also alkyl aryl acetylenes and thus enables to synthesize a wide range of all‐carbon tetrasubstituted alkenes. [ABSTRACT FROM AUTHOR]

A simple visible‐light‐induced CuCl‐catalyzed synthesis was developed for highly functionalized carbon‐centered compounds (α‐alk/aryloxy‐α‐diaryl/alkylaryl‐acetaldehydes/ketones) at room temperature using benzoquinone, alkyl/aryl alcohol, and alkyl/aryl terminal/internal alkynes. Late‐stage functionalized compounds show good antifungal activities, especially against Candida krusei fungal strain, in in vitro experiments (the Broth microdilution method). Moreover, toxicity tests (zebrafish egg model experiments) indicated that these compounds had negligible cytotoxicity. The green chemistry metrics (E‐factor value is 7.3) and eco‐scale (eco‐scale value is 58.8) evaluations show that the method is simple, mild, highly efficient, eco‐friendly, and environmentally feasible. [ABSTRACT FROM AUTHOR]

An efficient and facile synthesis of highly substituted pyridinium salts through the annulation of enamines with alkynes is reported herein. A Ag2CO3/HNTf2 synergistically acting catalyst system was developed and used in a condensation reaction between carbonyl substrates and propargylamine to afford structurally diverse pyridinium salts. A mechanistic investigation shows that this one‐pot transformation proceeded via selective 6‐endo‐dig cyclization of the in situ generated propargylenamine and protonolysis of the resulting vinyl–silver intermediate. The reaction conditions are mild, and the substrate scope is broad. During the cyclization, an unusual inversion of the normal reactivity of α,β‐unsaturated carbonyl systems was observed. [ABSTRACT FROM AUTHOR]

Computational studies on the electrophilic cyclization between alkynes and transient carbocations or Lewis‐acid‐activated epoxides show that the regiochemistry of the reaction depends on the terminal or internal position of the triple bond. Reactants possessing terminal alkynyl groups lead to six‐membered rings, whereas internal alkynes yield five‐membered rings through 6‐endo‐dig and 5‐exo‐dig electrophilic cyclizations, respectively. The regiochemistry of the reaction is not determined by two‐electron interactions, but by the minimization of Pauli repulsion. This scenario is preserved in related biomimetic reactions leading to steroid scaffolds. In this latter case, the stereochemistry of the cyclization reaction is oriented towards the formation of equatorial C−C bonds connecting the new six‐six‐ and six‐five‐membered fused rings. [ABSTRACT FROM AUTHOR]

Selective electrochemical hydrogenation of alkynes to alkenes under ambient conditions is a promising alternative to the traditional energy‐intensive and high‐cost thermocatalytic hydrogenation. However, the systematic summary on the electrocatalysts and electrolyzers remains lacked. Herein, we demonstrate a comprehensive review about recent achievements in the electrocatalysts including noble metal and non‐noble‐metal materials. Several effective strategies of catalyst design were developed to improve alkyne conversion, and alkene selectivity, for example, accelerating the formation of active hydrogen species, enhancing alkyne adsorption and suppressing the side reactions. Furthermore, the advantages and disadvantages of various electrolyzers are systematically discussed. Accordingly, major challenges and future trends in this field are proposed. [ABSTRACT FROM AUTHOR]

The reactivities of 2-butyne, cycloheptyne, cyclooctyne, and cyclononyne in the 1,3-dipolar cycloaddition reaction with methyl azide were evaluated through DFT calculations at the M06-2X/6-311++G(d)//M06-2X/6-31+G(d) level of theory. Computed activation free energies for the cycloadditions of cycloalkynes are 16.5-22.0 kcal mol-1 lower in energy than that of the acyclic 2-butyne. The strained or predistorted nature of cycloalkynes is often solely used to rationalize this significant rate enhancement. Our distortion/interaction-activation strain analysis has been revealed that the degree of geometrical predistortion of the cycloalkyne ground-state geometries acts to enhance reactivity compared with that of acyclic alkynes through three distinct mechanisms, not only due to (i) a reduced strain or distortion energy, but also to (ii) a smaller HOMO-LUMO gap, and (iii) an enhanced orbital overlap, which both contribute to more stabilizing orbital interactions.

A method for the synthesis of 4‐organoselanyl oxazinoindolone derivatives by the cascade cyclization of N‐(alkoxycarbonyl)‐2‐alkynylindoles using iron(III) chloride and diorganyl diselenides as promoters was developed. This protocol was applied to a series of N‐(alkoxycarbonyl)‐2‐alkynylindoles containing different substituents. The reaction conditions also tolerated a variety of diorganyl diselenides having both electron donating and electron withdrawing groups. However, the reaction did not work for diorganyl disulfides and ditellurides. The reaction mechanism seems to proceed via an ionic pathway and the cooperative action between iron(III) chloride and diorganyl diselenides is crucial for successful cyclization. We also found that using the same starting materials, by simply changing the electrophilic source to iodine, led to the formation of 4‐iodo‐oxazinoindolones. The high reactivity of Csp2−Se and Csp2−I bonds were tested under cross‐coupling conditions leading to the preparation of a new class of functionalized indole derivatives. In addition, the absorption, emission and electrochemical properties of 4‐organoselanyl oxazinoindolones showed an important relationship with the substituents of the aromatic rings. The advantages of the methodology include the use of electrophilic to promote the cyclization reaction and functionalization of the indole ring, and the electronic properties presented by the prepared compounds can be exploited as probes, analyte detectors and optical materials. [ABSTRACT FROM AUTHOR]

Polynucleotides, DNA and RNA (mRNA and non‐coding RNAs) are critically involved in the molecular pathways of disease. Small molecule binding interactions with polynucleotides can modify functional polynucleotide topologies and/or their interactions with proteins. Current approaches to library design (lead‐like or fragment‐like libraries) are based on protein‐ligand interactions and often include careful consideration of the 3‐dimensional orientation of binding motifs and exclude π‐rich compounds (polyfused aromatics) to avoid off‐target R/DNA interactions. In contrast to proteins, where π,π‐interactions are weak, polynucleotides can form strong π,π‐interactions with suitable π‐rich ligands. To assist in designing a polynucleotide‐biased library, a scaffold‐divergent synthesis approach to polyfused aromatic scaffolds has been undertaken. Initial screening hits that form moderately stable polynucleotide‐ligand‐protein ternary complexes can be further optimized through judicious incorporation of substituents on the scaffold to increase protein‐ligand interactions. An example of this approach is given for topoisomerase‐1 (TOP1), generating a novel TOP1 inhibitory chemotype. [ABSTRACT FROM AUTHOR]

The synthesis, characterization and catalytic activity of a new class of diruthenium hydrido carbonyl complexes bound to the tBuPNNP expanded pincer ligand is described. Reacting tBuPNNP with two equiv of RuHCl(PPh3)3(CO) at 140 °C produces an insoluble air‐stable complex, which was structurally characterized as [Ru2(tBuPNNP)H(μ‐H)Cl(μ‐Cl)(CO)2] (1) using solid‐state NMR, IR and X‐ray absorption spectroscopies and follow‐up reactivity. A reaction with KOtBu results in deprotonation of a methylene linker to produce [Ru2(tBuPNNP*)H(μ‐H)(μ‐OtBu)(CO)2] (3) featuring a partially dearomatized naphthyridine core. This enables metal‐ligand cooperative activation of H2 analogous to the mononuclear analogue, [Ru(tBuPNP*)H(CO)]. In contrast to the mononuclear system, the bimetallic analogue 3 catalyzes the E‐selective semi‐hydrogenation of alkynes at ambient temperature and atmospheric H2 pressure with good functional group tolerance. Monitoring the semi‐hydrogenation of diphenylacetylene by 1H NMR spectroscopy shows the intermediacy of Z‐stilbene, which is subsequently isomerized to the E‐isomer. Initial findings into the mode of action of this system are provided, including the spectroscopic characterization of a polyhydride intermediate and the isolation of a deactivated species with a partially hydrogenated naphthyridine backbone. [ABSTRACT FROM AUTHOR]