Hydroalkoxylation Of Alkynes Research Articles

Titanium-catalyzed highly stereoselective anti-Markovnikov intermolecular hydroalkoxylation of alkynes to prepare Z-enol ethers.

Enol ethers are essential synthetic frameworks and widely applied in organic synthesis; however, high regio- and stereo-selective access to enol ethers remains challenging. Herein, we report a titanium-catalyzed stereospecific anti-Markovnikov hydroalkoxylation reaction of alkynes for the synthesis of Z-enol ethers with excellent functional group tolerance and yields. Mechanistic studies showed that the titanium coordinates with the alkyne and then an oxygen anion attacks the π-bond of the alkyne from the backside to provide a trans-oxygen metallation intermediate, which accounts for the high Z-stereoselectivity. Furthermore, Z-enol ethers could be applied as a kind of synthon for late-stage transformations and gram-scale synthesis, which demonstrates their potential value in organic synthesis.

Visible-light induced metal-free intramolecular reductive cyclisations of ketones with alkynes and allenes.

A visible-light-induced, intramolecular, reductive cyclisation of ketones with an unsaturated hydrocarbon moiety was developed. In contrast to conventional protocols requiring resource precious or hazardous metal sources, this method enables facile access to ketyl radicals under metal-free and mild reaction conditions. By polarity-reversed, ketyl radical hydroalkoxylation of alkynes and allenes, a variety of five-membered (hetero-)cyclic products were generated in good yields with good to excellent stereoselectivities. The embedded homoallylic tertiary alcohol could be transformed into other useful functionalities, highlighting the synthetic utility of this reaction. This efficient and sustainable ketyl-alkyne/allene cross coupling also features broad functional group tolerance and scalability.

Synthesis of 1H-Isochromenes and 1,2-Dihydroisoquinolines by Indium(III)-Catalyzed Cycloisomerization of ortho-(Alkynyl)benzyl Derivatives

Abstract1H-Isochromenes and 1,2-dihydroisoquinolines are synthesized by regioselective indium(III)-catalyzed intramolecular hydrofunctionalization of o-(alkynyl)benzyl derivatives. The reaction with o-(alkynyl)benzyl alcohols and amines proceeds using indium triiodide (5–10 mol%) in toluene at 80–100 °C via regioselective 6-endo-dig intramolecular alkyne hydroalkoxylation or hydroamination in good yields. Alternatively, the cycloisomerization reaction of o-(alkynyl)benzaldehydes and imine derivatives using InI3 (5 mol%) and the Hantzsch ester (120 mol%) takes place, under milder reaction conditions, to give a variety of functionalized 1H-isochromenes and 1,2-dihydroisoquinolines through a domino cycloisomerization/reduction approach.

Transition Metal-Catalyzed Hydroalkoxylation of Alkynes: An Overview.

Oxygen-bearing motifs, mainly the congener heterocycles are ubiquitous due to their presence in various natural products and bioactive scaffolds. Although in literature, several strategies have been developed for their synthesis, hydroalkoxylation of alkynes has come forward as a method of choice and has been used extensively. In particular, hydroalkoxylation of alkynes has gained enormous attention from the synthetic community due to the rapid access to a very useful and reactive synthetic intermediate like 'enol ether'. Furthermore, to manifold the utility of these methods, reports have been developed elaborating the generation of 'enol ether' using hydroalkoxylation and their usage in various reactions in cascade or tandem manner. This review focuses on recent development on the hydroalkoxylation of alkynes for the synthesis of oxygen-containing entities.

Towards Dual-Metal Catalyzed Hydroalkoxylation of Alkynes

Poly (vinyl ethers) are compounds with great value in the coating industry due to exhibiting properties such as high viscosity, soft adhesiveness, resistance to saponification and solubility in water and organic solvents. However, the main challenge in this field is the synthesis of vinyl ether monomers that can be synthetized by methodologies such as vinyl transfer, reduction of vinyl phosphate ether, isomerization, hydrogenation of acetylenic ethers, elimination, addition of alcohols to alkyne species etc. Nevertheless, the most successful strategy to access to vinyl ether derivatives is the addition of alcohols to alkynes catalyzed by transition metals such as molybdenum, tungsten, ruthenium, palladium, platinum, gold, silver, iridium and rhodium, where gold-NHC catalysts have shown the best results in vinyl ether synthesis. Recently, the hydrophenoxylation reaction was found to proceed through a digold-assisted process where the species that determine the rate of the reaction are PhO-[Au(IPr)] and alkyne-[Au(IPr)]. Later, the improvement of the hydrophenoxylation reaction by using a mixed combination of Cu-NHC and Au-NHC catalysts was also reported. DFT studies confirmed a cost-effective method for the hydrophenoxylation reaction and located the rate-determining step, which turned out to be quite sensitive to the sterical hindrance due to the NHC ligands.

Gold(I)-Catalyzed Intramolecular Hydroamination and Hydroalkoxylation of Alkynes: Access to Original Heterospirocycles.

We report here a simple and robust gold-catalyzed annulation reaction, giving N- and O-spirocycles in good to excellent yields. We have prepared a library of protected amines and tertiary alcohols that give, upon cyclization with alkynes, a representative set of heterospirocycles and illustrate reaction compatibility with diverse functional groups. A change in catalytic activity is possible by modifying the solvent, and two original tricyclic spirocycles were synthesized in a tandem reaction.

Thiolate Bridged Gold(I)–NHC Catalysts: New Approach for Catalyst Design and its Application to Trapping Catalytic Intermediates

New dinuclear N-heterocyclic gold complexes with bridging thiolate ligands have been designed as catalytic precursors with desired properties such as stability, recyclability and that do not require additives. The dinuclear compound [(AuNHC)2 (μ-SC6 F5 )]OTf could slowly release the active catalytic species [Au(NHC)]+ and the precursor [Au(SC6 F5 )(NHC)] in solution, which means that both species would remain stable throughout the catalytic cycle and the pre-catalyst could easily be recovered. The properties exhibited by the complexes have been taken advantage of to gain new insights on the gold-catalyzed hydroalkoxylation of alkynes, with the aim of clarifying all the steps of the catalytic cycle, together with the characterization of intermediates and final products. Isolation and characterization of the pure final spiroketals and the thermodynamic intermediate have been achieved for the first time. Moreover, the kinetic intermediate has also been detected for the first time.

Ortho-Oxygenative 1,2-Difunctionalization of Diarylalkynes under Merged Gold/Organophotoredox Relay Catalysis.

Reported herein is an ortho-oxygenative 1,2-difunctionalization of diarylalkynes under merged gold/organophotoredox catalysis to access highly functionalized 2-(2-hydroxyaryl)-2-alkoxy-1-arylethan-1-ones. Detailed mechanistic studies suggested a relay process, initiating with gold-catalyzed hydroalkoxylation of alkynes, to generate enol-ether followed by a key formal [4+2]-cycloaddition reaction. The successful application of the present methodology was also shown for the synthesis of benzofurans.

Catalytic ring-closing reactions of gold compounds containing bis(phosphino)ferrocene ligands

The efficiency of various gold compounds containing bis(phosphino)ferrocene ligands for catalyzing ring-closing reactions was examined. Six commercially available bis(phosphino)ferrocene ligands: 1,1′-bis(ditert-butylphosphino)ferrocene (dtbpf), 1,1′-bis(diphenylphosphino)ferrocene (dppf), 1,1′-bis(dicylohexylphosphino)ferrocene (dcpf), 1,1′-bis(diiso-propylphosphino)ferrocene (dippf), 1-diphenylphosphino-1′-di-tert-butylphosphinoferrocene (dppdtbpf) and 1,1′-bis(5-methyl-2-furanylphosphino)ferrocene (dfurpf) were employed in this study. In addition to the previously reported [Au2Cl2(μ-PP)] (PP = dtbpf, dppf, dcpf, dippf or dppdtbpf) compounds, [Au2Cl2(μ-dfurpf)] was synthesized and characterized by NMR spectroscopy, cyclic voltammetry and X-ray crystallography. All of these gold compounds react with Na[BArF24] (BArF24 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) to remove a chloride and yield the cationic monochlorides, [Au2(μ-Cl)(μ-PP)]+. The effectiveness of the [Au2Cl2(μ-PP)] and [Au2(μ-Cl)(μ-PP)][BArF24], either pre-formed or generated in situ, compounds for the catalytic intramolecular alkyne hydroalkoxylation of (Z)-3-methylpent-2-en-4-yn-1-ol was examined in CDCl3 and toluene-d8. The ring-closing of N-(prop-2-yn-1-yl)benzamide was also examined and was efficiently carried out in toluene-d8 using [Au2(μ-Cl)(μ-PP)][BArF24] (PP = dtbpf, dppf, dcpf, dippf, dppdtbpf or dfurpf). In addition, [Au2Cl2(μ-dppe)] and [Au2(μ-Cl)(μ-dppe)][BArF24] were examined as catalysts for these ring-closing reactions in order to determine if the ferrocene backbone of the bis(phosphino)ferrocene ligands was important for catalysis.

Catalytic and metal-free intramolecular hydroalkoxylation of alkynes

Benzyltrimethylammonium hydroxide act as an efficient metal-free catalyst for the intramolecular hydroalkoxylation of alkynes. Notably, the use of microwave irradiation allowed reaction to operate in only two minutes. Under optimized reaction conditions, linear alkynes bearing aryl and heteroaryl substituents were successfully cyclized with good level of stereoselectivity.

Catalytic Reactions of Terminal Alkynes Using Rhodium(I) Complexes Bearing 8-Quinolinolate Ligands

8-Quinolinolate is a monoanionic, hard, strongly σ-donating ligand that can form strong chelates with various metals. However, studies of the catalytic activities of soft transition metal complexes such as greater than second row, low-valent, late-transition metals having 8-quinolinolate ligands had not been well explored until recently. In recent years, several research groups including our own have studied and developed various reactions of terminal alkynes using rhodium(I) catalysts containing an 8-quinolinolate ligand. In this Perspective, we surveyed the transformations of terminal alkynes using 8-quinolinolato rhodium(I) catalyst such as additions of alcohols, amines, and thiols as well as polymerization, trimerization, dimerization, and alkyne/alkene [2 + 2] cycloaddition. Mechanistic studies based on theoretical calculations of hydroalkoxylation of alkynes and alkyne/alkene [2 + 2] cycloaddition reactions have also been described.

A Fluorinated Cobalt(III) Porphyrin Complex for Hydroalkoxylation of Alkynes.

A fluorinated cobalt(III) porphyrin complex [Co(TPFPP)NTf2·2C2H5OH, where TPFPP=5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, Tf=CF3SO2] promotes hydroalkoxylation of alkynes to give acetals in good to excellent yields. The acetals can be directly functionalized with nucleophiles in a one-pot procedure.

Selective Gold Recovery and Catalysis in a Highly Flexible Methionine-Decorated Metal-Organic Framework.

A novel chiral 3D bioMOF exhibiting functional channels with thio-alkyl chains derived from the natural amino acid l-methionine (1) has been rationally prepared. The well-known strong affinity of gold for sulfur derivatives, together with the extremely high flexibility of the thioether "arms" decorating the channels, account for a selective capture of gold(III) and gold(I) salts in the presence of other metal cations typically found in electronic wastes. The X-ray single-crystal structures of the different gold adsorbates Au(III)@1 and Au(I)@1 suggest that the selective metal capture occurs in a metal ion recognition process somehow mimicking what happens in biological systems and protein receptors. Both Au(III)@1 and Au(I)@1 display high activity as heterogeneous catalyst for the hydroalkoxylation of alkynes, further expanding the application of these novel hybrid materials.

Correction: Regioselectivity in the Au-catalyzed hydration and hydroalkoxylation of alkynes.

Correction for 'Regioselectivity in the Au-catalyzed hydration and hydroalkoxylation of alkynes' by Justin A. Goodwin et al., Chem. Commun., 2015, 51, 8730-8741.

Hydroalkoxylation of alkynes by a nitroxyl containing alcohol, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl: synthesis of spin-labeled enol ethers

Hydroalkoxylation of alkynes by a nitroxyl containing alcohol, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl: synthesis of spin-labeled enol ethers

Explanation of “Silver Effects” in Gold(I)-Catalyzed Hydroalkoxylation of Alkynes

An extensive experimental NMR study of gold-catalyzed hydroalkoxylation was conducted to explain the influence of a silver salt additive on the gold-catalyzed process (silver effect). Addition of silver salt may have no effect or a negative or positive effect on gold-catalyzed hydroalkoxylation. However, silver was shown to be essentially innocent (plays no role) with regard to the mechanism of the catalytic process itself. The effect occurs only if silver induces variations in the fraction of in-cycle organogold intermediates and H+. This is associated with the formation of the argento vinyl gold species G, which was shown to be an off-cycle intermediate. This species is formed by trapping the vinyl gold species B with Ag+; in the same way, the diaurated species D (another possible off-cycle intermediate) is formed by trapping B with LAu+. The argento vinyl gold species G1 was extensively characterized in solution by various NMR techniques at different temperatures. Furthermore, bringing together our res...

Intermolecular Hydroalkoxylation of Terminal Alkynes Catalyzed by a Dipyrrinato Rhodium(I) Complex with Unusual Selectivity

An operationally simple and atom-economical method for the E-selective preparation of enol ethers is described. A novel dicarbonyl(5-phenyldipyrrinato)rhodium complex, 2, was prepared in four synthetic steps, characterized by X-ray crystallography and NMR spectroscopy, and then investigated as a catalyst for the intermolecular hydroalkoxylation of terminal alkynes. Solvent and substrate studies were used to gain insight into the mechanism of the reaction. Cyclic voltammetry was also used to investigate the electronic properties of 2. The rhodium(I)-catalyzed intermolecular alkyne hydroalkoxylation reaction reported here mediates excellent substrate transformation with a high degree of E/Z selectivity which is opposite to that reported previously using alternative catalysts.

ChemInform Abstract: Regioselectivity in the Au‐Catalyzed Hydration and Hydroalkoxylation of Alkynes

AbstractReview: [51 refs.

Gold(I)-Catalyzed Asymmetric Hydroalkoxylation of Alkynes

Gold(I)-Catalyzed Asymmetric Hydroalkoxylation of Alkynes

Regioselectivity in the Au-catalyzed hydration and hydroalkoxylation of alkynes.

Over the past decade and a half, homogenous gold catalysis has emerged as a diverse and rich field of research resulting in the continuous development of new methods for organic synthesis. The activation of alkynes towards nucleophilic attack by Au(I) and Au(III) complexes is a well-established mode of reactivity and the gold-catalyzed hydration and hydroalkoxylation of alkynes are two of the more well-explored reaction pathways. Although these classes of reactions have seen continuous development since their initial reports, achieving regioselectivity persists as one of the most challenging issues for this chemistry. This article aims to draw attention to the general problem of regioselectivity in these reactions. A select set of examples is presented to highlight the challenges and survey some of the strategies employed to address this problem.