Aromatic Terminal Alkynes Research Articles

Copper‐Catalyzed Enantioselective Hydrophosphorylation of Unactivated Alkynes

P‐stereogenic phosphorus compounds are essential across various fields, yet their synthesis via enantioselective P‐C bond formation remains both challenging and underdeveloped. We report the first copper‐catalyzed enantioselective hydrophosphorylation of alkynes, facilitated by a newly designed chiral 1,2‐diamine ligand. Unlike previous methods that rely on kinetic resolution with less than 50% conversion, our approach employs a distinct dynamic kinetic asymmetric transformation mechanism, achieving complete conversion of racemic starting materials. This reaction is compatible with a broad range of aromatic and aliphatic terminal alkynes, producing products with high yields (up to 95%), exclusive cis selectivity, and exceptional regio‐ and enantioselectivity (> 20:1 r.r. and up to 96% ee). The resulting products were further transformed into a diverse array of enantioenriched P‐stereogenic scaffolds. Preliminary mechanistic studies were conducted to elucidate the reaction details.

Copper-Catalyzed Enantioselective Hydrophosphorylation of Unactivated Alkynes.

P-stereogenic phosphorus compounds are essential across various fields, yet their synthesis via enantioselective P-C bond formation remains both challenging and underdeveloped. We report the first copper-catalyzed enantioselective hydrophosphorylation of alkynes, facilitated by a newly designed chiral 1,2-diamine ligand. Unlike previous methods that rely on kinetic resolution with less than 50% conversion, our approach employs a distinct dynamic kinetic asymmetric transformationmechanism, achieving complete conversion of racemic starting materials. This reaction is compatible with a broad range of aromatic and aliphatic terminal alkynes, producing products with high yields (up to 95%), exclusive cis selectivity, and exceptional regio- and enantioselectivity (> 20:1 r.r. and up to 96% ee). The resulting products were further transformed into a diverse array of enantioenriched P-stereogenic scaffolds. Preliminary mechanistic studies were conducted to elucidate the reaction details.

Hydromethylthiolation of alkynes via nucleophilic addition of dimethyl disulfide in DMSO

A hydromethylthiolation method for various alkynes has been developed using dimethyl disulfide as a source of the nucleophilic methylthiolate anion in a DMSO/EtOH or DMSO/H2O solvent system, with KOH as the base. For terminal aromatic alkynes, the reactions predominantly yield (Z)-anti-Markovnikov hydromethylthiolation products. The ratio of anti-Markovnikov to Markovnikov products typically exceeds 10:1, while the ratio of (Z)- to (E)-anti-Markovnikov products usually surpasses 7:1. In contrast, terminal aliphatic alkynes primarily produce Markovnikov hydromethylthiolation products. Reactions of internal aromatic alkynes also successfully produce the corresponding hydromethylthiolation products, whereas internal aliphatic alkynes do not exhibit reactivity in this system. The proposed mechanism suggests that in a basic DMSO solvent system, each equivalent of dimethyl disulfide is converted into two equivalents of methylthiolate anion. This anion then undergoes nucleophilic addition to the alkyne substrates, yielding hydromethylthiolation products. The regioselectivity and stereoselectivity of the hydromethylthiolation are influenced by the stability of the vinyl carbanion intermediate. Additionally, this method is also applicable to the hydrothiolation of alkynes using other disulfides.

Ambient Semi‐Hydrogenation of Terminal Alkynes with NaBH4 Catalyzed by Palladium Nanowires

AbstractThe semi‐hydrogenation of terminal alkynes is achieved with sodium borohydride (NaBH4) as the reductant and palladium nanowires (PdNWs) as the catalysts under ambient conditions. The reaction proceeds smoothly in the presence of only 0.32 mol % of PdNWs, giving the hydrogenated products with up to 98 % overall yields, in which 97 % are semi‐hydrogenated products. Under the optimal reaction conditions, both aromatic and aliphatic terminal alkynes have been successfully converted to the corresponding olefins with high efficiency and good selectivity. This method promotes the hydrogenation of terminal alkynes under mild conditions and opens up a window for the application of metal nanowires in organic syntheses.

Copper-Catalyzed Alkynylation of In Situ-Generated Azoalkenes: An Umpolung Approach to Pyrazoles.

A straightforward umpolung approach to regioselectively N-protected polysubstituted pyrazoles starting from aromatic α-halohydrazones and terminal alkynes has been developed. In this process, azoalkenes generated in situ from α-halohydrazones are involved in the Cu(I)-catalyzed Michael addition with alkynes to give α-alkynyl-substituted hydrazones that cyclize to give the target pyrazoles in 37-85% yield. The method employs readily available starting materials and features good functional group compatibility (nitro, sulfonyl, cyano, trimethylsilyl, and primary bromoalkyl groups, esters, and alcohols are tolerated) and scalability.

CuBr-Catalyzed Coupling of Propargyl Bromides with Terminal Alkynes: Syntheses of 1,4-Diynes and Alkynyl Shift Access to Unsymmetrical 1, n-Diynes.

A CuBr-catalyzed cross-coupling reaction of propargyl bromides with terminal alkynes for the synthesis of 1, n-diynes was investigated. In N,N-dimethylacetamide (DMAc), the cross-coupling reactions of 3-bromo-1-arylpropynes, 3-bromo-1-phenyl-butyne/pentyne with aromatic terminal alkynes in the presence of CuBr and K3PO4 under nitrogen at 40 °C occur to give 1, 5-diaryl-1, 4-diynes having 3-CH2/3-CHMe/3-CHEt/3-CHiPr moieties with high chemoselectivity. Under similar reaction conditions, either the reactions of 3-bromo-1-arylpropynes with aliphatic terminal alkynes or the reactions of 3-bromo-1-alkylpropynes with aromatic terminal alkynes afforded the unexpected unsymmetric 1, 4-disubstituted 1, 3-diynes through one of the alkynyl group shifts to the side conjugating with the aryl group; in these cases, 1, 5-disubstituted 1, 4-diynes could not be obtained at all. In addition, when 3-bromo-1-phenyl-butynes react with aliphatic terminal alkynes bearing a distal phenyl group, the formed 1, 4-diynes are expected not to undergo the alkynyl group shift due to the methyl group at 3-position to form 1, 3-diynes; however, 1, 4-diynes could not be obtained either, and the 1, 5-, 1, 6-, and 1, 7-diynes, by an unprecedented remote alkynyl shift to the side conjugating with the aryl group, were isolated from the reaction mixtures in good yields.

Photocatalytic Terminal C-C Coupling Reaction Inside Water Soluble Nanocages.

Developing methods that activate C-H bonds directly with high selectivity for C-C bond formation in complex organic synthesis has been a major chemistry challenge. Recently it has been shown that photoactivation of weakly polarized C-H bonds can be carried out inside a cationic water-soluble nanocage with visible light-mediated host-guest charge transfer (CT) chemistry. Using this novel photoredox activation paradigm, here we demonstrate C-C bond formation to photo-generate 1,3-diynes at room temperature in water from terminal aromatic alkynes for the first time. The formation of cavity-confined alkyne radical cation and the proton-removed neutral radical species highlight the unique C-C coupling step driven by supramolecular preorganization.

Photocatalytic Terminal C−C Coupling Reaction Inside Water Soluble Nanocages

AbstractDeveloping methods that activate C−H bonds directly with high selectivity for C−C bond formation in complex organic synthesis has been a major chemistry challenge. Recently it has been shown that photoactivation of weakly polarized C−H bonds can be carried out inside a cationic water‐soluble nanocage with visible light‐mediated host‐guest charge transfer (CT) chemistry. Using this novel photoredox activation paradigm, here we demonstrate C−C bond formation to photo‐generate 1,3‐diynes at room temperature in water from terminal aromatic alkynes for the first time. The formation of cavity‐confined alkyne radical cation and the proton‐removed neutral radical species highlight the unique C−C coupling step driven by supramolecular preorganization.

A general palladium‐catalyzed carbonylation synthesis of aurones with aryl bromides using CO2

AbstractA general and efficient strategy synthesis of aurones by carbonylation reaction of aryl bromides and terminal aromatic alkynes using CO2 has been established. Various terminal aromatic alkynes and 2‐bromophenol by using CO2 with hydrosilane could be leveraged to provide various aurones in good yields under mild reaction conditions. Moreover, palladium‐catalyzed carbonylation reaction mechanism is proposed for the preparation of aurones.

A Simple and Practical Bis-N-Heterocyclic Carbene as an Efficient Ligand in Cu-Catalyzed Glaser Reaction.

Conjugated diyne derivatives are important scaffolds in modern organic synthetic chemistry. Using the Glaser reaction involves the coupling of terminal alkynes which can efficiently produce conjugated diyne derivatives, while the use of a stoichiometric amount of copper salts, strong inorganic base, and excess oxidants is generally needed. Developing an environmentally friendly and effective method for the construction of symmetrical 1,3-diynes compounds by Glaser coupling is still highly desirable. In this study, we present an economical method for the production of symmetric diynes starting from various terminal acetylenes in a Glaser reaction. A simple and practical bis-N-heterocyclic carbene ligand has been introduced as efficient ligands for the Cu-catalyzed Glaser reaction. High product yields were obtained at 100 °C for a variety of substrates including aliphatic and aromatic terminal alkynes and differently substituted terminal alkynes including the highly sterically hindered substrate 2-methoxy ethynylbenzene or 2-trifluoromethyl ethynylbenzene and a series of functional groups, such as trifluoromethyl group, ester group, carboxyl group, and nitrile group. The established protocol is carried out in air under base-free condition and is operationally simple. These research work suggest that bis-N-heterocyclic carbene could also an appealing ligand for Glaser reaction and provide a reference for the preparation of symmetric 1,3-diynes in industrial filed.

Palladium-Catalyzed Carbonylation for General Synthesis of Aurones Using CO2.

The carbonylation of alkynes using CO2 to generate aurones is to date unknown. In this study, a palladium-catalyzed carbonylation of terminal aromatic alkynes and the waste hydrosilane, poly(methylhydrosiloxane) (PMHS), is carried out with 2-iodophenol using CO2 to produce aurones. A variety of terminal alkynes and substituted 2-iodophenols are transformed into aurones in good yields. Preliminary mechanistic studies indicate that silyl formate, generated from CO2 and PMHS, plays a crucial role in the carbonylation reaction.

Palladium-catalyzed Sonogashira coupling to synthesis of gem‑difluoroenynes

Herein, we developed the palladium-catalyzed Sonogashira-type cross-coupling of 1‑bromo-2,2-difluoroethylene with a variety of aromatic and aliphatic terminal alkynes proceeds smoothly at mild reaction condition to access the corresponding gem‑difluoroenyne derivatives. 1-Bromo-2,2-difluoroethylene is a useful difluoroethenyl source because of its commercially available and easy-to-handle. This new synthetic protocol provided a novel strategy to directly construct gem‑difluoroenynes with good functional group tolerance and high yields.

Rhodium-Catalyzed Anti-Markovnikov Transfer Hydroiodination of Terminal Alkynes.

A rhodium-catalyzed anti-Markovnikov hydroiodination of aromatic and aliphatic terminal alkynes is reported. Depending on the choice of ligand and substrate, either (E)- or (Z)-configured alkenyl iodides are obtained in high to exclusive isomeric purity. The reaction exhibits a broad substrate scope and high functional group tolerance, employing easily accessible or commercially available aliphatic iodides as HI surrogates through a shuttle process. The synthesized vinyl iodides were applied in several C-C and C-heteroatom bond-forming reactions with full retention of the stereoselectivity. The developed method could be used to significantly shorten the total synthesis of a marine cis-fatty acid. Additionally, initial deuterium-labeling experiments and stoichiometric reactions shed some light on the potential reaction mechanism.

Rhodium‐katalysierte Anti‐Markovnikov Hydroiodierung von Terminalen Alkinen**

AbstractWir beschreiben eine Rhodium‐katalysierte anti‐Markovnikov Hydroiodierung von terminalen aromatischen und aliphatischen Alkinen. Je nach Wahl des Liganden und Substrats werden entweder (E)‐ oder (Z)‐konfigurierte Alkenyliodide mit hoher bis ausschließlicher Isomerenreinheit erhalten. Die Reaktion weist ein breites Substratspektrum und eine hohe Toleranz gegenüber funktionellen Gruppen auf, wobei leicht zugängliche oder kommerziell erhältliche aliphatische Iodide als HI‐Äquivalent via einem Shuttle‐Prozess verwendet werden. Die synthetisierten Vinyliodide wurden in mehreren Reaktionen zur Bildung von C−C und C−Heteroatom Bindungen unter vollständiger Beibehaltung der Stereoselektivität eingesetzt. Mit der entwickelten Methode konnte die Totalsynthese einer marinen cis‐Fettsäure deutlich verkürzt werden. Zusätzlich konnten mithilfe von Deuterium‐Markierungsexperimenten und stöchiometrischen Reaktionen erste Informationen über einen möglichen Reaktionsmechanismus erhalten werden.

Copper(I)-Catalyzed Syntheses of Benzo[b]fluorenes by the Cascade Reactions of 2-Alkynylbenzaldehyde N-Tosylhydrazones and Aromatic Terminal Alkynes.

Benzo[b]fluorenes were synthesized via CuI-catalyzed cascade reactions of 2-alkynylbenzaldehyde N-tosylhydrazones and aromatic terminal alkynes in the presence of base including the formation of the benzoenyne-allene intermediate in situ and its Schmittel cyclization. Density functional theory calculation was performed to give the energy difference for the formation of 5-phenyl-11H-benzo[b]fluorene and 1,2-diphenyl-1H-cyclobuta[a]indene from the proposed diradical intermediates.

Organosuperbase-Catalyzed 1,1-Diboration of Alkynes

1,1-Diboryl alkenes are versatile building blocks in organic synthesis and medicinal chemistry. However, there have been only a small number of established methods to prepare this class of compounds, and most of them used transition-metal catalysts, which are undesirable in the preparation of biologically relevant compounds. Herein, we report an unprecedented application of P1–tBu phosphazene as a superbasic organocatalyst to promote 1,1-diboration reactions of unactivated aromatic and electron-deficient terminal alkynes. The dual Brønsted and Lewis basicity of this phosphazene enables the activation of reaction substrates and allows for high regio- and stereoselectivity to be obtained. A combination of thorough experimental and computational studies suggests interesting mechanistic insights for these phosphazene-catalyzed diboration reactions, which are also discussed in detail.

Zinc (II) complex immobilized on the surface of magnetic nanoparticles modified with phenanthroline: A novel and efficient nanomagnetic reusable catalyst for cross-coupling reaction of aryl iodides with terminal aromatic alkynes

A novel and green nanomagnetic zinc catalyst were fabricated via the immobilization of zinc (II) complex on the surface of magnetic nanoparticles modified with phenanthroline (MNPs-Phen-Zn(II)). The structure of MNPs-Phen-Zn(II) nanomaterial was characterized by a series of spectroscopic techniques including FT-IR spectroscopy, SEM, TEM, EDX, XRD, VSM, and ICP-OES. The resulting zinc nanomagnetic catalyst was shown high catalytic activity for the synthesis of disubstituted alkynes via C(sp2)–C(sp) cross-coupling reactions of alkynes with aryl iodides under eco-friendly conditions. To the best of our knowledge, it is the first report on the utilization of zinc nanomagnetic catalyst for the Sonogashira type cross-coupling reaction of alkynes with aryl iodides in the absence of added Pd and Cu sources. The simple preparation of the catalyst from commercially available materials, excellent chemoselectivity, easy separation of products, and straightforward recovery and reusability of the catalyst with unaltered activity make our procedure a green and practical method.

Searching for highly active cobalt catalysts bearing Schiff base ligands for Markovnikov-selective hydrosilylation of alkynes with tertiary silanes

The search for simple and easy-to-synthesize ligands for bench stable cobalt (pre)catalysts that would ensure high activity and selectivity in alkyne hydrosilylation reactions is an interesting current challenge. Herein, we report that a cobalt(II) complex bearing pyrimidine-imine-2H-imidazole ligand activated by LiHBEt3 exhibits not only high catalytic activity, but also unprecedented tolerance towards tertiary silanes in highly regioselective Markovnikov hydrosilylation of aliphatic and aromatic terminal alkynes to give α-vinylsilanes. In addition, a variety of 1-aryl-2-(trimethylsilyl)acetylenes have been hydrosilylated efficiently by diphenylsilane in the presence of [Co(L)Cl2]/LiHBEt3 catalytic system to yield (E)-1-aryl-1,2-bis(silyl)ethenes with high selectivity. Such selectivity is very rarely observed for cobalt-catalyzed hydrosilylation of silylacetylenes.

Palladium‐Catalyzed Tail‐to‐Tail Reductive Dimerization of Terminal Alkynes to 2,3‐Dibranched Butadienes

AbstractThe palladium‐catalyzed tail‐to‐tail reductive dimerization of terminal alkynes is described for the first time. Aromatic terminal alkynes bearing diverse and sensitive functional groups as well as aliphatic terminal alkynes are efficiently transformed to 2,3‐dibranched butadienes. The key to achieve a selective tail‐to‐tail reductive dimerization reaction is to control appropriately the acidity of the reaction solution, which is accomplished by a combined use of pivalic acid and para‐toluenesulfonic acid. The tail‐to‐tail reductive dimerization reaction is proposed to proceed via a cationic alkenyl palladium intermediate under acidic conditions.

Palladium-Catalyzed Tail-to-Tail Reductive Dimerization of Terminal Alkynes to 2,3-Dibranched Butadienes.

The palladium-catalyzed tail-to-tail reductive dimerization of terminal alkynes is described for the first time. Aromatic terminal alkynes bearing diverse and sensitive functional groups as well as aliphatic terminal alkynes are efficiently transformed to 2,3-dibranched butadienes. The key to achieve a selective tail-to-tail reductive dimerization reaction is to control appropriately the acidity of the reaction solution, which is accomplished by a combined use of pivalic acid and para-toluenesulfonic acid. The tail-to-tail reductive dimerization reaction is proposed to proceed via a cationic alkenyl palladium intermediate under acidic conditions.