Activation Of Alkynes Research Articles

Gold-Catalyzed Diyne-Ene Annulation for the Synthesis of Polysubstituted Benzenes through Formal [3+3] Approach with Amide as the Critical Co-Catalyst.

The one-step synthesis of tetra-substituted benzenes was accomplished via gold-catalyzed diyne-ene annulation. Distinguished from prior modification methods, this novel strategy undergoes formal [3+3] cyclization, producing polysubstituted benzenes with exceptional efficiency. The critical factor enabling this transformation was the introduction of amides, which were reported for the first time in gold catalysis as covalent nucleophilic co-catalysts. This interesting protocol not only offers a new strategy to achieve functional benzenes with high efficiency, but also enlightens potential new reaction pathways within gold-catalyzed alkyne activation processes.

Regiodivergent Gold-Catalyzed Rearrangement-Addition Reactions of Sulfenylated Propargylic Carboxylates with Indoles.

Sulfenylated propargylic carboxylates were introduced to investigate the influence of sulfur substitution in gold-catalyzed alkyne activation pathways. Regiodivergent gold-catalyzed rearrangement and indole capture reactions proceed under mild conditions to give functionalized indole products bearing sulfenylated (Z)-enol carboxylate motifs. Pathways involving both 1,2- and 1,3-carboxylate migrations are achieved selectively, with indole being added in a 1,4 relationship to the sulfenyl group in each case. High levels of selectivity are influenced by the catalyst system, counterion, and carboxylate group.

Differential Activation of Alkynes between Capped and Naked Ag Nanoclusters Anchored by Highly-Open Mesoporous CeO2 for Two Coupling Reactions with CO2.

The cyclization of 3-hydroxy alkynes and the carboxylation of terminal alkynes both with CO2 are two attractive strategies to simultaneously reduce CO2 emission and produce value-added chemicals. Herein, the differential activation of alkynes over atomically precise Ag nanoclusters (NCs) supported on Metal-organic framework-derivedhighly-open mesoporous CeO2 (HM-CeO2) by reserving or removing their surface captopril ligands is reported. The ligand-capped Ag NCs possess electron-rich Ag atoms as efficient π-activation catalytic sites in cyclization reactions, while the naked Ag NCs possess partial positive-charged Ag atoms as perfect σ-activation catalytic sites in carboxylation reactions. Impressively, via coupling with HM-CeO2 featuring abundant basic sites and quick mass transfer, the ligand-capped Ag NCs afford 97.9% yield of 4,4-dimethyl-5-methylidene-1,3-dioxolan-2-one for the cyclization of 2-methyl-3-butyn-2-ol with CO2, which is 4.5 times that of the naked Ag NCs (21.7%), while the naked Ag NCs achieve 98.5% yield of n-butyl 2-alkynoate for the carboxylation of phenylacetylene with CO2, which is 15.6 times that of ligand-capped Ag NCs (6.3%). Density functional theory calculations reveal the ligand-capped Ag NCs can effectively activate alkynyl carbonate ions for the intramolecular ring closing in cyclization reaction, while the naked Ag NCs are highly affiliative in stabilizing terminal alkynyl anions for the insertion of CO2 in carboxylation reaction.

Constructing Pd and Cu Crowding Single Atoms by Protein Confinement to Promote Sonogashira Reaction.

For multicenter-catalyzed reactions, it is important to accurately construct heterogeneous catalysts containing multiple active centers with high activity and low cost, whichis more challenging compared to homogeneous catalysts because of the low activity and spatial confinement of active centers in the loaded state. Herein, a convenient protein confinement strategy is reported to locate Pd and Cu single atoms in crowding state on carbon coated alumina for promoting Sonogashira reaction, the most powerful method for constructing the acetylenic moiety in molecules. The single-atomic Pd and Cu centers take advantage in not only the maximized atomic utilization for low cost, but also the much-enhanced performance by facilitating the activation of aryl halides and alkynes. Their locally crowded dispersion brings them closer to each other, which facilitates the transmetallation process of acetylide intermediates between them. Thus, the Sonogashira reaction is drove smoothly by the obtained catalyst with a turnover frequency value of 313 h-1, much more efficiently than that by commercial Pd/C and CuI catalyst, conventional Pd and Cu nanocatalysts, and mixed Pd and Cu single-atom catalyst. The obtained catalyst also exhibits the outstanding durability in the recycling test.

Gold‐Catalyzed Diyne‐Ene Annulation for the Synthesis of Polysubstituted Benzenes through Formal [3+3] Approach with Amide as the Critical Co‐Catalyst

The one‐step synthesis of tetra‐substituted benzenes was accomplished via gold‐catalyzed diyne‐ene annulation. Distinguished from prior modification methods, this novel strategy undergoes formal [3+3] cyclization, producing polysubstituted benzenes with exceptional efficiency. The critical factor enabling this transformation was the introduction of amides, which were reported for the first time in gold catalysis as covalent nucleophilic co‐catalysts. This interesting protocol not only offers a new strategy to achieve functional benzenes with high efficiency, but also enlightens potential new reaction pathways within gold‐catalyzed alkyne activation processes.

Cover Feature: The Noble Addendum of a Phosphenium Ligand to a Base Metal: Coordination, Activation, and Hydrogenation of Alkenes and Alkynes on a Chromium Complex (ChemPlusChem 6/2024)

Cover Feature: The Noble Addendum of a Phosphenium Ligand to a Base Metal: Coordination, Activation, and Hydrogenation of Alkenes and Alkynes on a Chromium Complex (ChemPlusChem 6/2024)

Synthesis of a Side Chain Alkyne Analogue of Sitosterol as a Chemical Probe for Imaging in Plant Cells.

Clickable chemical tools are essential for studying the localization and role of biomolecules in living cells. For this purpose, alkyne-based close analogs of the respective biomolecules are of outstanding interest. Here, in the field of phytosterols, we present the first alkyne derivative of sitosterol, which fulfills the crucial requirements for such a chemical tool as follows: very similar in size and lipophilicity to the plant phytosterols, and correct absolute configuration at C-24. The alkyne sitosterol FB-DJ-1 was synthesized, starting from stigmasterol, which comprised nine steps, utilizing a novel alkyne activation method, a Johnson-Claisen rearrangement for the stereoselective construction of a branched sterol side chain, and a Bestmann-Ohira reaction for the generation of the alkyne moiety.

The Noble Addendum of a Phosphenium Ligand to a Base Metal: Coordination, Activation, and Hydrogenation of Alkenes and Alkynes on a Chromium Complex.

The synthesis of a new bis-NHP complex (NHP=N-heterocyclic phosphenium) of chromium via salt metathesis and studies of its reactivity are reported. Photochemical reactions with H2 and selected olefins give rise to non-isolable H2- and π-alkene complexes identified spectroscopically, while internal alkynes react via activation of the triple bond to yield isolable metalla-phospha-cyclobutenes characterized by spectroscopic and XRD data. DFT studies give a preliminary account of the bonding in H2- and alkene-complexes and explain the different reactivity towards alkenes and alkynes as the consequence of kinetic effects. Photolysis of the bis-NHP-complex in the presence of H2 and olefins or alkenes enables the catalytic hydrogenation of the organic substrates, while the π-ethene complex mediates the catalytic hydrogenation of ethene in a dark reaction. The similarities and differences between both catalytic processes are shortly discussed.

Pd-Catalyzed Chelation-Assisted Regioselective and Site Selective Cyclative C-H Annulation of Alkynyl Oximes with Activated Alkynes.

Electrophilic cyclization and concomitant C-H annulation constitute an expedient cascade strategy for the construction of multicyclic scaffolds with precise substitutional patterns. We report here a novel Pd-catalyzed cyclative annulation of ynone oxime with activated alkynes. The cascade features a dual regioselectivity including site selective C-H activation and chelation-assisted selective insertion of alkynes. Control experiments together with kinetic experiments give insights into the mechanism.

In Situ Activation of Azaarenes and Terminal Alkynes to Construct Bridged Polycyclic Compounds Containing Isoquinolinones.

A copper-catalyzed [4+2] cyclization reaction of isoquinolines and alkynes is developed for the one-step construction of isoquinolinone derivatives with multisubstituted bridging rings. The unique feature of this three-component tandem cyclization reaction is the functionalization of the C1, N2, C3, and C4 positions of 3-haloisoquinolines via the construction of new C-N, C═O, and C-C bonds. This dearomatization strategy for the synthesis of structurally complex isoquinolinone-bridged cyclic compounds offers good chemoselectivity, broad functional group compatibility, greenness, and high step economy.

Boron Trifluoride-Mediated Domino Dehydration/Electrophilic Cyclization of Silylalkynols Leading to 2,3-Fused Tricyclic Benzofulvenes.

A BF3-mediated domino dehydration/electrophilic cyclization of silylalkynols to form 2,3-fused tricyclic benzofulvenes was achieved. In the latter step, in situ generated BF3·OH2 enables the electrophilic activation of alkynes. The predominant Z-selectivity of the reaction is also discussed.

Expedient alkyne semi-hydrogenation by using a bimetallic AgCu-C3N4 single atom catalyst.

Metal-catalyzed semi-hydrogenation of alkynes is an important step in organic synthesis to produce diverse chemical compounds. However, conventional noble metal catalysts often suffer from poor selectivity owing to over-hydrogenation. Here, we demonstrate a high-loading bimetallic AgCu-C3N4 single-atom catalyst (SAC) for alkyne semi-hydrogenation. The AgCu-C3N4 SACs exhibit higher activity and selectivity (99%) than their low-loading variants due to the synergistic interaction of heteronuclear Ag-Cu sites at small inter-site distances. Using a combination of techniques such as phenylacetylene-DRIFTS, H2-temperature programmed desorption and DFT calculations, we showed that the cooperative bimetallic interaction during alkyne semi-hydrogenation was achieved by isolated Ag centers as hydrogen activation sites and isolated Cu centers as alkyne activation sites. Our work highlights the importance of achieving high catalyst loading to reduce the inter-site distance in bimetallic SACs for cooperative interactions, which can potentially open new catalytic pathways for synthesizing fine chemicals and pharmaceuticals.

Kaskadenreaktionen von aryl‐substituierten terminalen Alkinen unter Beteiligung von in situ erzeugten α‐Imino‐Goldcarbenen

AbstractWir berichten über eine effiziente, hochselektive und divergente Synthesemethode zur Herstellung von 2‐substituierten Indolen und aryl‐anellierten Carbazolen über die intermolekulare Erzeugung von α‐Imino‐Goldcarbenen aus terminalen Alkinen oder Diinen in Kombination mit Sulfiliminen. Wichtig ist, dass die Tandemreaktion durch eine intermolekulare Goldcarbenbildung/C−H‐ Anellierung, gefolgt von der Aktivierung eines zweiten Alkins, die zu einer 6‐endo‐dig‐Zyklisierung führt, abläuft, was sich deutlich von früheren Ansätzen der dualen Aktivierung oder 1,6‐Carbenverschiebung für Diin‐Systeme unterscheidet. Im Falle von ortho‐Alkinylanilin als Ausgangsmaterial wurde eine unerwartete regioselektive Bildung der Indolkomponente über den intermolekularen Weg anstelle einer intramolekularen Hydroaminierung entdeckt. Diese Reaktivität ebnete den Weg für eine Eintopfsynthese des 11H‐Indolo‐[3,2‐c]‐Chinolin‐Gerüsts, indem das gebildete Aminoindol für eine anschließende Pictet–Spengler‐Reaktion mit Aldehyden genutzt wurde. Die photophysikalischen Eigenschaften der Carbazole zeigten eine gute violett‐blaue Emission mit Quantenausbeuten von bis zu 40 %.

Cascade Reactions of Aryl-Substituted Terminal Alkynes Involving in Situ-Generated α-Imino Gold Carbenes.

An efficient, highly selective and divergent synthetic method to construct 2-substituted indoles and aryl-annulated carbazoles via the intermolecular generation of α-imino gold carbenes from terminal alkynes or diynes in combination with sulfilimines is disclosed. Importantly, the tandem reaction is proposed to proceed through an intermolecular gold carbene generation/C-H annulation followed by the activation of a second alkyne leading to 6-endo-dig cyclization, which is significantly different from previous dual activation or 1,6-carbene shift approaches for diyne systems. In the case of ortho-alkynylaniline as starting material, an unexpected regioselective formation of the indole moiety via the intermolecular path, instead of intramolecular hydroamination was discovered. This reactivity paved the way for a one-pot synthesis of the 11H-indolo [3,2-c] quinoline scaffold by exploiting the formed amino indole for a subsequent Pictet-Spengler reaction with aldehydes. The photophysical properties of the carbazoles indicated good violet-blue emission with quantum yields up to 40 %.

In Situ Anchoring of Small-Sized Silver Nanoparticles on Porphyrinic Triazine-Based Frameworks for the Conversion of CO2 into α-Alkylidene Cyclic Carbonates with Outstanding Catalytic Activities under Ambient Conditions.

The preparation of catalytic hybrid materials by introducing highly dispersed metallic nanoparticles into porous organic polymers (POPs) may be an ideal and promising strategy for integrated CO2 capture and conversion. In terms of the carboxylative cyclization of propargyl alcohols with CO2, the anchoring of silver nanoparticles (AgNPs) on functional POPs to fabricate efficient heterogeneous catalysts is considered to be quite intriguing but remains challenging. In the contribution, well-dispersed AgNPs were successfully anchored onto the porphyrinic triazine-based frameworks by a simple "liquid impregnation and in situ reduction" strategy. The presence of N-rich dual active sites, porphyrin and triazine, which acted as the electron donor and acceptor, respectively, offered a huge opportunity for the nucleation and growth of metal nanoparticles. Significantly, the as-prepared catalyst Ag/TPP-CTF shows excellent catalytic activity (up to 99%) toward the carboxylative cyclization of propargyl alcohols with CO2 at room temperature, achieving record-breaking activities (TOF up to 615 h-1 at 1 bar and 3077 h-1 at 10 bar). Moreover, the catalyst can be easily recovered and reused at least 10 times with retention of high catalytic activity. The possible mechanism involves small-sized AgNP-mediated alkyne activation, which may promote highly efficient and green conversion of CO2. This work paves the way for immobilizing metal nanoparticles onto functional POPs by surface structure changes for enhanced CO2 catalysis.

Four - Electron Oxidative Addition of an N=N Double Bond at a Chromium Metallocyclopropene.

This report describes the synthesis of a pseudo-tetrahedral chromium alkyne complex supported by a bidentate phosphinimide ligand and its reactivity with azobenzene. Characterization of the former by structural and computational methods reveals an unprecedented extent of alkyne activation by a formal chromium(II) center, suggesting that this complex is best described as a chromium(IV)-metallocyclopropene. Exposure of this compound to an azobenzene derivative results in the formation of a chromium(VI) diimido complex, which constitutes a rare 4-electron oxidative addition of an N=N double bond. The isolation of a chromium(IV)-hydrazido intermediate enabled mechanistic investigations of this challenging bond cleavage process. This work substantiates the notion that terminal phosphinimide ligands can engender first-row transition metal ions with exceptional reactivity.

Four – Electron Oxidative Addition of an N=N Double Bond at a Chromium Metallocyclopropene

This report describes the synthesis of a pseudo‐tetrahedral chromium alkyne complex supported by a bidentate phosphinimide ligand and its reactivity with azobenzene. Characterization of the former by structural and computational methods reveals an unprecedented extent of alkyne activation by a formal chromium(II) center, suggesting that this complex is best described as a chromium(IV)‐metallocyclopropene. Exposure of this compound to an azobenzene derivative results in the formation of a chromium(VI) diimido complex, which constitutes a rare 4‐electron oxidative addition of an N=N double bond. The isolation of a chromium(IV)‐hydrazido intermediate enabled mechanistic investigations of this challenging bond cleavage process. This work substantiates the notion that terminal phosphinimide ligands can engender first‐row transition metal ions with exceptional reactivity.

Recent Progress in Gold‐Catalyzed Reactions of Alkynes for the Construction of Indole Frameworks

AbstractIndole heterocycles hold an important position in chemical landscape because of their prominence in natural products and pharmaceuticals. Consequently, development of new and efficient strategies to access indole scaffold are of continuous interest. For the past few years, gold‐catalyzed activation of alkyne has emerged as a powerful strategy for constructing the heterocyclic skeleton. The present review highlights recent advances (2018–2023) toward synthesis of indole skeletons via gold‐catalyzed annulations of alkynes. A variety of alkynes, such as, ynamides, azido alkynes, ortho‐alkynyl anilines, propargylic alcohols, ortho‐alkynyl phenylimines, and miscellaneous alkynes are employed affording various indole architectures under gold catalysis. Moreover, mechanisms are included in most of the cases for better understanding of the reaction pathway.

Cyclization, Decyclization, and Metallacyclization of Pyridine-Substituted Homopropargylic Alcohols on Ruthenium(II) and Osmium(II) Centers.

Systematic investigations on the reactions between cis-[M(dppm)2 Cl2 ] (M=Ru/Os; dppm=1,1-bis(diphenylphosphino)methane) and pyridine/quinoline substituted homopropargylic alcohols uncovered the diverse Ru(II)/Os(II)-induced alkyne activation pathways. The alkynes underwent cyclization on M via a "non-vinylidene" pathway at lower temperatures, resulting in alkenyl intermediates which might further metallacyclize to give metallapyrroloindolizines. Conversely, reactions at higher temperatures induced alkyne cyclization on M via a "vinylidene" pathway, affording cyclic oxacarbene complexes. Additionally, a rare decyclization mechanism was observed during the transformation of a metallacyclization-resistant alkenyl complex into a cyclic oxacarbene complex. DFT calculations were employed to validate the experimental findings. Overall, these results not only provide insights into controlling alkyne activation pathways, but also offer new strategies for preparing metalated heterocyclic and metallacyclic complexes.

Recent Advances in the Gold-Catalyzed Reactions of Propargyl Esters.

ConspectusLate-transition-metal-based complexes represent an indispensable catalytic tool in chemical synthesis due to their ability to increase molecular complexity rapidly and efficiently from readily accessible substrates in a single operation. Added to this is the exquisite control of product chemo-, diastereo-, enantio-, and site-selectivities achieved by catalytic systems of the transition-metal salts that have been developed to mediate a wide range of functional group transformations. Within this venerable synthetic toolbox, complexes and salts of Au(I) and Au(III) have emerged in recent years as an invaluable addition as a result of their potent σ- and π-Lewis acidities and ability to stabilize cationic reaction intermediates. The insights provided by mechanistic studies examining the various electronic, steric, and stereoelectronic factors at play in the organogold species that are expected to be formed in the catalytic chemistry of the transition-metal complex have also been pivotal in understanding and exploring their potential synthetic utility. Illustrative of this, for example, is the contribution made by the gold-catalyzed cycloisomerization chemistry of propargyl esters in synthetic strategies to a variety of bioactive natural products and compounds of current pharmaceutical and materials interest. This Account summarizes our efforts over the past decade toward realizing new single-step strategies for carbocyclic and heterocyclic synthesis that relied on the gold-catalyzed reactions of propargyl esters. It outlines synthetic methods developed by the group that exploited the unique reactivities of the gold-carbene species typically generated from the [2,3]-sigmatropic rearrangement of the compound class containing a terminal or electron-deficient alkyne moiety on exposure to the transition-metal salt. This Account also describes the realization of synthetic methods initiated by the gold-catalyzed 1,3-acyloxy migration of propargyl esters with an electronically unbiased disubstituted C≡C bond that delivers the corresponding allenyl ester that is primed for further reactivity on activation by the group 11 metal complex. The studies formed a part of an ongoing overarching program within our group that was focused on determining reactivities in gold catalysis that would enable their application as readily recognizable disconnections in retrosynthetic analysis. They were additionally a part of efforts aimed at evaluating the opportunities offered by the relativistic effects possessed by a Au(I) and Au(III) complex, the most pronounced among the d-block elements and thus the catalyst of choice in alkyne activation chemistry, to generate new chemical space. For instance, we demonstrated in several studies the cycloisomerization of 1,3- and 1,4-enyne esters to be a reliable strategy for the in situ formation of a wide range of 1,4-cyclopentadienyl derivatives. Their further reaction with an appropriately placed functional group or a second starting material was then shown to afford a variety of synthetic targets containing the five-membered ring structure. An example of this was the assembly of a new member of the 1H-isoindole compound family that was found to exhibit potent TNF-α (tumor necrosis factor-α) inhibitor activity.