Alkyne Metathesis Research Articles

Total Synthesis of the Biphenyl Alkaloid (−)‐Lythranidine

A sequence comprising a ring-closing alkyne metathesis of a propargyl alcohol derivative, followed by a ruthenium-catalyzed redox isomerization of the derived cycloalkyne and a transannular aza-Michael addition allowed the formation of the distinguishing piperidine-metacyclophane framework of the Lythraceum alkaloid lythanidine in a few high-yielding steps. This application attests to the excellent functional-group tolerance of a molybdenum alkylidyne complex endowed with triphenylsilanolate ligands, which enabled the macrocyclization even in the presence of protic functionalities, and thus illustrates the power of contemporary catalytic acetylene chemistry for target-oriented synthesis.

Dynamic covalent chemistry approaches toward macrocycles, molecular cages, and polymers.

The current research in the field of dynamic covalent chemistry includes the study of dynamic covalent reactions, catalysts, and their applications. Unlike noncovalent interactions utilized in supramolecular chemistry, the formation/breakage of covalent bonding has slower kinetics and usually requires the aid of a catalyst. Catalytic systems that enable efficient thermodynamic equilibrium are thus essential. In this Account, we describe the development of efficient catalysts for alkyne metathesis, and discuss the application of dynamic covalent reactions (mainly imine, olefin, and alkyne metathesis) in the development of organic functional materials. Alkyne metathesis is an emerging dynamic covalent reaction that offers robust and linear acetylene linkages. By introducing a podand motif into the catalyst ligand design, we have developed a series of highly active and robust alkyne metathesis catalysts, which, for the first time, enabled the one-step covalent assembly of ethynylene-linked functional molecular cages. Imine chemistry and olefin metathesis are among the most well-established reversible reactions, and have also been our main synthetic tools. Various shape-persistent macrocycles and covalent organic polyhedrons have been efficiently constructed in one-step through dynamic imine chemistry and olefin metathesis. The geometrical features and solubilizing groups of the building blocks as well as the reaction kinetics have significant effect on the outcome of a covalent assembly process. More recently, we explored the orthogonality of imine and olefin metatheses, and successfully synthesized heterosequenced macrocycles and molecular cages through one-pot orthogonal dynamic covalent chemistry. In addition to discrete molecular architectures, functional polymeric materials can also be accessed through dynamic covalent reactions. Defect-free solution-processable conjugated polyaryleneethynylenes and polydiacetylenes have been prepared through alkyne metathesis polymerization. We prepared imine- or ethynylene-linked porous polymer networks, which exhibit permanent porosity with high specific surface areas. Our most recent contribution is the discovery of a recyclable polyimine material whose self-healing can be activated simply by heating or water treatment. The facile access to complex functional organic molecules through dynamic covalent chemistry has allowed us to explore their exciting applications in gas adsorption/separation, host-guest chemistry, and nanocomposite fabrication. It is clear that there are significant opportunities for improved dynamic covalent systems and their more widespread applications in materials science.

ChemInform Abstract: Transition Metal Complexes Supported by Highly Basic Imidazolin‐2‐iminato and Imidazolin‐2‐imine N‐Donor Ligands

AbstractReview: 186 refs.

Tungsten and Molybdenum 2,4,6‐Trimethylbenzylidyne Complexes as Robust Pre‐Catalysts for Alkyne Metathesis

AbstractA series of 2,4,6‐trimethylbenzylidyne tungsten and molybdenum complexes was prepared from the tribromides mer‐[MesCMBr3(dme)] (9a, M=W; 9b, M=Mo, dme=1,2‐dimethoxyethane). Successive reaction of complexes 9 with lithium or potassium hexafluoro‐tert‐butoxide and lithium 1,3‐di‐tert‐butylimidazolin‐2‐imide, (Imt‐BuN)Li, afforded the imidazolin‐2‐iminato complexes [MesCM{OC(CF3)2Me}2(Imt‐BuN)] (10a, M=W; 10b, M=Mo), whereas the reactions of 9 with three equivalents of LiOSi(O‐t‐Bu)3 or KOC(CF3)3 gave [MesCM{OSi(O‐t‐Bu)3}3] (11a, M=W; 11b, M=Mo) and [MesCM{OC(CF3)3}3] (12a, M=W; 12b, M=Mo), respectively. For comparison, the benzylidyne complex [PhCMo{OSi(O‐t‐Bu)3}3] (7b) was also prepared, and its molecular structure together with those of 10a, 10b, 11b, 12a and 12b were established by X‐ray diffraction analysis. Complexes 10 and 11 were employed as pre‐catalysts for the alkyne metathesis of the test substrate 3‐pentynyl benzyl ether (13) at low catalyst loadings (1 mol%) in the presence of molecular sieve (5 Å). Comparative studies of these 2,4,6‐trimethylbenzylidyne species (MesCM) with their benzylidyne analogues (PhCM) revealed that the increased steric bulk renders the former more stable and manageable in air in solid form for shorter periods of time, but at the expense of a slower initiation, which requires higher temperatures or longer reaction times.magnified image

ChemInform Abstract: Intramolecular Transannulation of Alkynyl Triazoles via Alkyne—Carbene Metathesis Step: Access to Fused Pyrroles.

An intramolecular Rh-catalyzed transannulation reaction of alkynyl triazoles has been developed. This method allows efficient construction of various 5,5-fused pyrroles, including tetrahydropyrrolo and spiro systems. The method demonstrates excellent functional group compatibility. A rhodium carbene–alkyne metathesis mechanism is proposed for this transformation.

Identification and Synthesis of Macrolide Pheromones of the Grain Beetle Oryzaephilus Surinamensis and the Frog Spinomantis Aglavei

Macrolide lactones, the so called cucujolides derived from unsaturated fatty acids, are aggregation pheromones of cucujid grain beetles. Thirty years ago, Oehlschlarger et al. showed that (3Z,6Z)-dodeca-3,6-dien-11-olide (4) and the respective 12-olide (7) attract the sawtoothed grain beetle Oryzaephilus surinamensis, whereas (5Z,8Z,13R)-tetradeca-5,8-dien-13-olide (5) increases the response synergistically. The frass of this beetle is attractive for its parasitoid Cephalonomia tarsalis, which potentially can be used for pest control. A GC/MS analysis of attractive frass showed the presence of 5, together with an unknown isomer. Cucujolide V was tentatively identified also in the femoral glands, pheromone-releasing structures, of the Madagascan mantelline frog Spinomantis aglavei. Therefore, a new route to synthesize doubly unsaturated macrolides allowing the flexible attachment of the side chain was developed. A straightforward method to obtain Z configured macrolides involves ring-closing alkyne metathesis (RCAM) followed by Lindlar-catalyzed hydrogenation. This methodology was extended to homoconjugated diene macrolides by using RCAM after introduction of one Z configured double bond in the precursor by Wittig reaction. A tungsten benzylidyne complex was used as the catalyst in the RCAM reaction, which afforded the products in high yield at room temperature. With the synthetic material at hand, the unknown isomer was identified as the new natural product (5Z,8Z,12R)-tetradeca-5,8-dien-12-olide, cucujolide X (8). Furthermore, the route also allowed the synthesis of cucujolide V in good yield. The natural products were identified by the synthesis of enantiomerically pure or enriched material and gas chromatography on chiral phases. The new macrolide (R)-8 proved to be biologically active, attracting female O. surinamensis, but no males. The synthetic material allowed the identification of (R)-5 in both the beetle and the frog.

ChemInform Abstract: Increasing the Structural Span of Alkyne Metathesis.

AbstractSeveral new catalysts for alkyne metathesis, e.g. MMC, are introduced.

ChemInform Abstract: Expanding the Scope of Metathesis: A Survey of Polyfunctional, Single‐Site Supported Tungsten Systems for Hydrocarbon Valorization

AbstractReview: 122 refs.

NHC-coordinated silagermenylidene functionalized in allylic position and its behaviour as a ligand

Vinylidenes are common in transition metal chemistry with catalytic applications in alkene and alkyne metathesis. We report here the isolation of a heavier analogue of vinylidene, an α-chlorosilyl functionalized silagermenylidene stabilized by an N-heterocyclic carbene (NHC). Silagermenylidene (Tip2Cl)Si-(Tip)Si=Ge·NHC(iPr2Me2) (4-E/Z; Tip = 2,4,6-(i)Pr3C6H2; NHC(iPr2Me2) = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) is available as an E/Z-equilibrium mixture from Tip2Si=Si(Tip)Li and NHC(iPr2Me2)·GeCl2. Reaction of 4-E/Z with Fe2(CO)9 affords a silagermenylidene Fe(CO)4 complex, which slowly isomerizes to its E-isomer at 25 °C. A rearranged Fe(CO)3 complex with an allylic SiGeSi ligand is obtained as a side product at 65 °C.

Application of alkyne metathesis in polymer synthesis

Alkyne metathesis has attracted growing attention in the past two decades as a versatile synthetic method for formation of the CC bond. It has been applied to the synthesis of various small organic molecules, linear polymers, as well as polymer networks. Herein, we review the recent progress in the development of alkyne metathesis polymerization, which includes acyclic diyne metathesis polymerization (ADIMET) and ring-opening alkyne metathesis polymerization (ROAMP).

Conjugated BODIPY DYEmers by Metathesis Reactions

Boron dipyrrin (BODIPY) DYEmers bridged by conjugating ethynylene and ethenylene moieties can be prepared through metal-promoted metathesis reactions. Alkyne metathesis was advantageous over alkene metathesis and Stille coupling for BODIPY substrates, but also showed specific restrictions with respect to steric encumbrance and regioselectivity. All derivatives with unhindered rotations along the bridges reside in a coplanar minimum conformation. For a hindered β-ethenylene-bridged DYEmer, the shifts in the (1) H NMR spectrum indicate a significant loss of coplanarity and conjugation. The electronic interactions of the BODIPY subchromophores, visualized by optical spectra and cyclic voltammograms, deviate significantly from those found for nonconjugated and excitonically coupled DYEmers. The observed properties can be rationalized in each case by the respective strength of conjugation through the α or β position, the degree of coplanarity, and conformational dynamics.

ChemInform Abstract: Metathesis Reactions: Recent Trends and Challenges

AbstractReview: 273 refs.

Inhibitory Effect of Ethylene in Ene–Yne Metathesis: The Case for Ruthenacyclobutane Resting States

Reaction kinetics and mechanistic studies for ethylene-internal alkyne metathesis promoted by the phosphine-free initiator Ru1 (Piers's catalyst) is described. The kinetic order of reactants and catalyst was determined. The effect of ethylene was studied at different solution concentrations using ethylene gas mixtures applied at constant pressure. Unlike earlier studies with the second-generation Grubbs complex, ethylene was found to show an inverse first-order rate dependence. Under catalytic conditions, a ruthenacyclobutane intermediate was observed by proton NMR spectroscopy at low temperature. Combined with the kinetic study, these data suggest a catalytic cycle involving a reactive L(n)Ru═CH2 species in equilibrium with ethylene to form a ruthenacyclobutane, a catalyst resting state. Rates were determined for a variety of internal alkynes of varying substitution. Also, at low ethylene pressures, preparative syntheses of several 2,3-disubstituted 1,3-butadienes were achieved. Using the kinetic method, several phosphine-free inhibitors were examined for their ability to promote ethylene-alkyne metathesis and to guide selection of the optimal catalyst.

Teaching Metathesis “Simple” Stereochemistry

Applications of metal-catalyzed olefin metathesis reactions manifested dramatic growth during the late 20th and early 21st centuries, culminating in the 2005 Nobel Prize awarded to three of the pioneers. The standard catalysts developed during that time frame and their descendants have profoundly changed the mindset of the synthetic community, even though they do not provide a handle to control selectivity issues as fundamental as the E/Z geometry of the newly formed double bond. With yet another generation of catalysts in the making that are far superior in this regard, a new wave seems to be building up that is expected to have enormous impact, too. The current state of the art is critically assessed, as are possible alternatives such as the metathesis of triple bonds followed by stereoselective semi-reduction.

Porous Poly(aryleneethynylene) Networks through Alkyne Metathesis

The development of new synthetic methods has been a central challenge in the field of organic porous materials. Herein, we present the first application of alkyne metathesis to the synthesis of highly porous poly(aryleneethynylene) (PAE) networks. The permanent porosity of as-synthesized PAEs was confirmed by N2 adsorption/desorption studies, and high Brunauer–Emmett–Teller (BET) specific surface areas (P/P0 = 0.01–0.1) up to 2312 m2·g–1 were observed. PAE networks with the same chemical connectivity were also prepared through palladium-catalyzed Sonogashira cross-coupling under otherwise similar reaction conditions. The networks prepared through alkyne metathesis at three different temperatures (40 °C, 55 °C, and 75 °C) consistently exhibit a higher specific surface area and higher thermal stability, suggesting alkyne metathesis is advantageous in the preparation of highly porous organic materials. Our study demonstrates the feasibility of employing alkyne metathesis in the preparation of porous polymer networks and serves to expand the synthetic tool box for this emerging class of porous materials.

Increasing the Structural Span of Alkyne Metathesis

A new generation of alkyne metathesis catalysts, which are distinguished by high activity and an exquisite functional group tolerance, allows the scope of this transformation to be extended beyond its traditional range. They accept substrates that were previously found problematic or unreactive, such as propargyl alcohol derivatives, electron-deficient and electron-rich acetylenes of various types, and even terminal alkynes. Moreover, post-metathetic transformations other than semi-reduction increase the structural portfolio, as witnessed by the synthesis of a annulated phenol derivative via ring-closing alkyne metathesis (RCAM) followed by a transannular gold-catalyzed Conia-ene reaction. Further examples encompass a post-metathetic transannular ketone-alkyne cyclization with formation of a trisubstituted furan, a ruthenium-catalyzed redox isomerization, and a Meyer-Schuster rearrangement/oxa-Michael cascade. These reaction modes fueled model studies toward salicylate macrolides, furanocembranolides, and the cytotoxic macrolides acutiphycin and enigmazole A; moreover, they served as the key design elements of concise total syntheses of dehydrocurvularin (27) and the antibiotic agent A26771B (36).

Metathesis Reactions: Recent Trends and Challenges

AbstractMetathesis reactions are now essential for the synthesis of complex organic molecules; a large variety of useful materials are available, and progress in this field is growing rapidly. Emphasis in this review on metathesis is placed on the recent developments of stereoselectivity aspects by using new families of molybdenum (Schrock type) and ruthenium (Grubbs type) catalysts for olefin metathesis. Recent progress in alkyne metathesis catalysts (Fürstner type) and their properties and impressive synthetic applications are highlighted as well as new terminal alkyne metathesis catalysts (Tamm type). The various strategies involved in recovering the catalyst and removing metal impurities from products towards “green chemistry” are briefly reviewed. The relationship of olefin metathesis is shown with the alkyne metathesis reaction that was exploited by Fürstner, with alkane metathesis that was achieved by using surface organometallic chemistry and highlighted by Basset, and with the use of classic organometallic catalysts by the Goldman and Brookhart groups. Finally, recent developments in polymer chemistry that involve stereochemical control, low polydispersities, and applications are summarized.

ChemInform Abstract: Alkyne Metathesis by Molybdenum and Tungsten Alkylidyne Complexes

AbstractReview: 33 refs.

Silica-Supported Molybdenum Nitride for Alkyne Metathesis

Key words molybdenum nitride - alkyne metathesis - silica-supported catalysts

Syntheses and Properties of Graphyne Fragments: Trigonally Expanded Dehydrobenzo[12]annulenes

We present herein the synthesis and properties of the largest hitherto unknown graphyne fragment, namely trigonally expanded tetrakis(dehydrobenzo[12]annulene)s (tetrakis-DBAs). Intramolecular three-fold alkyne metathesis reactions of hexakis(arylethynyl)DBAs 9 a and 9 b using Fürstner's Mo catalyst furnished tetrakis-DBAs 8 a and 8 b substituted with tert-butyl or branched alkyl ester groups in moderate and fair yields, respectively, demonstrating that the metathesis reaction of this protocol is a powerful tool for the construction of graphyne fragment backbones. For comparison, hexakis(arylethynyl)DBAs 9 c-g have also been prepared. The one-photon absorption spectrum of tetrakis-DBA 8 a bearing tert-butyl groups revealed a remarkable bathochromic shift of the absorption cut-off (λcutoff ) compared with those of previously reported graphyne fragments due to extended π-conjugation. Moreover, in the two-photon absorption spectrum, 8 a showed a large cross-section for a pure hydrocarbon because of the planar para-phenylene-ethynylene conjugation pathways. Hexakis(arylethynyl)-DBAs 9 c-e and 9 g and tetrakis-DBA 8 b bearing electron-withdrawing groups aggregated in chloroform solutions. Comparison between the free energies of 9 e and 8 b bearing the same substituents revealed the more favorable association of the latter due to stronger π-π interactions between the extended π-cores. Polarized optical microscopy observations, DSC, and XRD measurements showed that 8 b and 9 e with branched alkyl ester groups displayed columnar rectangular mesophases. By the time-resolved microwave conductivity method, the columnar rectangular phase of 8 b was shown to exhibit a moderate charge-carrier mobility of 0.12 cm(2) V(-1) s(-1) . These results indicate that large graphyne fragments can serve as good organic semiconductors.