Effect of Support on Metathesis of n‐Decane: Drastic Improvement in Alkane Metathesis with WMe5 Linked to Silica–Alumina

[WMe₆] ( 1 ) supported on the surface of SiO₂–Al₂O₃₍₅₀₀₎ ( 2 ) has been extensively characterized by solid‐state NMR spectroscopy, elemental analysis, and gas quantification, which clearly reveal the formation of a mixture of monopodal and bipodal species with the migration of methyl from W to Al. The supported species SiO₂–Al₂O₃₍₅₀₀₎ ( 2 ) transformed at 120 °C into two types of carbynic centers, one of which is cationic and the other neutral. These species are very efficient for the metathesis of n‐decane. Comparison with already‐synthesized neutral bipodal tungsten indicates that the high increase in activity is due to the cationic character of the grafted tungsten.     

Cationic Silica‐Supported N‐Heterocyclic Carbene Tungsten Oxo Alkylidene Sites: Highly Active and Stable Catalysts for Olefin Metathesis

Designing supported alkene metathesis catalysts with high activity and stability is still a challenge, despite significant advances in the last years. Described herein is the combination of strong σ‐donating N‐heterocyclic carbene ligands with weak σ‐donating surface silanolates and cationic tungsten sites leading to highly active and stable alkene metathesis catalysts. These well‐defined silica‐supported catalysts, [(≡SiO)W(=O)(=CHCMe₂Ph)(IMes)(OTf)] and [(≡SiO)W(=O)(=CHCMe₂Ph)(IMes)⁺][B(Ar^F)₄^?] [IMes=1,3‐bis(2,4,6‐trimethylphenyl)‐imidazol‐2‐ylidene, B(Ar^F)₄=B(3,5‐(CF₃)₂C₆H₃)₄] catalyze alkene metathesis, and the cationic species display unprecedented activity for a broad range of substrates, especially for terminal olefins with turnover numbers above 1.2 million for propene.     

Linker‐Free,Silica‐Bound Olefin‐Metathesis Catalysts: Applications in Heterogeneous Catalysis

A set of heterogenized olefin‐metathesis catalysts, which consisted of Ru complexes with the H₂ITap ligand (1,3‐bis(2′,6′‐dimethyl‐4′dimethyl aminophenyl)‐4,5‐dihydroimidazol‐2‐ylidene) that had been adsorbed onto a silica support, has been prepared. These complexes showed strong binding to the solid support without the need for tethering groups on the complex or functionalized silica. The catalysts were tested in the ring‐opening–ring‐closing‐metathesis (RO‐RCM) of cyclooctene (COE) and the self‐metathesis of methyl oleate under continuous‐flow conditions. The best complexes showed a TON>4000, which surpasses the previously reported materials that were either based on the Grubbs–Hoveyda II complex on silica or on the classical heterogeneous Re₂O₇/B₂O₃ catalyst.     

Alkyne Metathesis on the Rise

The early years of alkyne metathesis were marked by a somewhat ironic state of affairs: the proposed mechanism was swiftly validated and more than one effective catalyst became available shortly after the discovery of this transformation; surprisingly, however, the impact on synthesis remained very limited for a long period of time. Recent advances, however, suggest that this situation is about to change: the remarkable activity, functional‐group tolerance, and reliability of the latest generation of catalysts open the door for highly advanced applications. The resulting (cyclo)alkynes are amenable to numerous postmetathetic transformations, which diversify the product portfolio and bring many different structural motifs into reach. Since the catalysts have also evolved from the glovebox to the benchtop, there should be little barrier left for a wider use of this reaction in organic synthesis.     

Well-Defined Alkyne Metathesis Catalysts: Developments and Recent Applications

Although alkyne metathesis has been known for 50 years, rapid progress in this field has mostly occurred during the last two decades. In this article, the development of several highly efficient and thoroughly studied alkyne metathesis catalysts is reviewed, which includes novel well-defined, in situ formed and heterogeneous systems. Various alkyne metathesis methodologies, including alkyne cross-metathesis (ACM), ring-closing alkyne metathesis (RCAM), cyclooligomerization, acyclic diyne metathesis polymerization (ADIMET), and ring-opening alkyne metathesis polymerization (ROAMP), are presented, and their application in natural product synthesis, materials science as well as supramolecular and polymer chemistry is discussed. Recent progress in the metathesis of diynes is also summarized, which gave rise to new methods such as ring-closing diyne metathesis (RCDM) and diyne cross-metathesis (DYCM).     

Highly Active Multidentate Ligand‐Based Alkyne Metathesis Catalysts

Alkyne metathesis catalysts composed of molybdenum(VI) propylidyne and multidentate tris(2‐hydroxylbenzyl)methane ligands have been developed, which exhibit excellent stability (remains active in solution for months at room temperature), high activity, and broad functional‐group tolerance. The homodimerization and cyclooligomerization of monopropynyl or dipropynyl substrates, including challenging heterocycle substrates (e.g., pyridine), proceed efficiently at 40–55 °C in a closed system. The ligand structure and catalytic activity relationship has been investigated, which shows that the ortho groups of the multidentate phenol ligands are critical to the stability and activity of such a catalyst system.     

Well‐Defined Silica‐Supported Mo–Alkylidene Catalyst Precursors Containing One OR Substituent: Methods of Preparation and Structure–Reactivity Relationship in Alkene Metathesis

Silica supports : Well‐defined silica‐supported Mo–alkylidene complexes containing one alkoxy/aryloxy substituent are selectively obtained by grafting onto silica either well‐defined molecular bis(alkoxy) or alkoxyamido complexes (see scheme). These silica‐supported complexes are highly efficient catalyst precursors for the metathesis of acyclic alkenes. However, they display poor performances in ring‐closing metathesis reactions, possibly due to the relatively large siloxy ligand (silica) inducing a greater rigidity.

     

Solid‐State NMR and DFT Studies on the Formation of Well‐Defined Silica‐Supported Tantallaaziridines: From Synthesis to Catalytic Application

Single‐site, well‐defined, silica‐supported tantallaaziridine intermediates [≡Si‐O‐Ta(η²‐NRCH₂)(NMe₂)₂] [R=Me ( 2 ), Ph ( 3 )] were prepared from silica‐supported tetrakis(dimethylamido)tantalum [≡Si‐O‐Ta(NMe₂)₄] ( 1 ) and fully characterized by FTIR spectroscopy, elemental analysis, and ¹H,¹³C HETCOR and DQ TQ solid‐state (SS) NMR spectroscopy. The formation mechanism, by β‐H abstraction, was investigated by SS NMR spectroscopy and supported by DFT calculations. The C?H activation of the dimethylamide ligand is favored for R=Ph. The results from catalytic testing in the hydroaminoalkylation of alkenes were consistent with the N‐alkyl aryl amine substrates being more efficient than N‐dialkyl amines.     

Catalytic Oxo/Imido Heterometathesis by a Well‐Defined Silica‐Supported Titanium Imido Complex

Grafting Ti(=NtBu)(Me₂Pyr)₂(py)₂ (Me₂Pyr= 2,5‐dimethylpyrrolyl, py=pyridine) onto the surface of silica partially dehydroxylated at 700 °C gives the well‐defined silica‐supported Ti imido complex (≡SiO)Ti(=NtBu)(Me₂Pyr)(py)₂, which is fully characterized by IR and solid‐state NMR spectroscopy as well as elemental and mass balance analyses. While stoichiometric imido‐transfer reactivity is typical for Ti imides, the obtained surface complex is unique in that it enables catalytic transformations involving Ti imido and oxo intermediates. In particular, it efficiently catalyzes imidation of carbonyl compounds with N‐sulfinylamines by oxo/imido heterometathesis.     

Formal Total Synthesis of Kendomycin by Way of Alkyne Metathesis/Gold Catalysis

In an attempt to study the ability of the latest generation of alkyne metathesis catalysts to process sterically hindered substrates, two different routes to the bacterial metabolite kendomycin ( 1 ) were explored. Whereas the cyclization of the overcrowded arylalkyne 39 and related substrates turned out to be impractical or even impossible, ring closure of the slightly relaxed diyne 45 was achieved in excellent yield under notably mild conditions with the aid of the molybdenum alkylidyne 2 endowed with triphenylsilanolate ligands. The resulting cycloalkyne 46 was engaged into a gold‐catalyzed hydroalkoxylation, which led to benzofuran 47 that had already previously served as a late‐stage intermediate en route to 1 .     

183W NMR Spectroscopy Guides the Search for Tungsten Alkylidyne Catalysts for Alkyne Metathesis

Triarylsilanolates are privileged ancillary ligands for molybdenum alkylidyne catalysts for alkyne metathesis but lead to disappointing results and poor stability in the tungsten series. ¹H,¹⁸³W heteronuclear multiple bond correlation spectroscopy, exploiting a favorable ⁵J-coupling between the ¹⁸³W center and the peripheral protons on the alkylidyne cap, revealed that these ligands upregulate the Lewis acidity to an extent that the tungstenacyclobutadiene formed in the initial [2+2] cycloaddition step is over-stabilized and the catalytic turnover brought to a halt. Guided by the ¹⁸³W NMR shifts as a proxy for the Lewis acidity of the central atom and by an accompanying chemical shift tensor analysis of the alkylidyne unit, the ligand design was revisited and a more strongly π-donating all-alkoxide ligand prepared. The new expanded chelate complex has a tempered Lewis acidity and outperforms the classical Schrock catalyst, carrying monodentate tert-butoxy ligands, in terms of rate and functional-group compatibility.     

Switching on the Metathesis Activity of Re Oxo Alkylidene Surface Sites through a Tailor‐Made Silica–Alumina Support

Re oxo alkylidene surface species are putative active sites in classical heterogeneous Re‐based alkene‐metathesis catalysts. However, the lack of evidence for such species questions their existence and/or relevance as reaction intermediates. Using Re(O)(=CH‐CH=CPh₂)(OtBu_F6)₃(THF), the corresponding well‐defined Re oxo alkylidene surface species can be generated on both silica and silica–alumina supports. While inactive on the silica support, it displays very good activity, even for functionalized olefins, on the silica–alumina support.     

Cyclooctane Metathesis Catalyzed by Silica‐Supported Tungsten Pentamethyl [(SiO)W(Me)5]: Distribution of Macrocyclic Alkanes

Metathesis of cyclic alkanes catalyzed by the new surface complex [(?SiO)W(Me)₅] affords a wide distribution of cyclic and macrocyclic alkanes. The major products with the formula C_nH_2n are the result of either a ring contraction or ring expansion of cyclooctane leading to lower unsubstituted cyclic alkanes (5≤n≤7) and to an unprecedented distribution of unsubstituted macrocyclic alkanes (12≤n≤40), respectively, identified by GC/MS and by NMR spectroscopies.     

Cross‐Metathesis of Terminal Alkynes

Terminal acetylenes are amongst the most problematic substrates for alkyne metathesis because they tend to undergo rapid polymerization on contact with a metal alkylidyne. The molybdenum complex 3 endowed with triphenylsilanolate ligands, however, is capable of inducing surprisingly effective cross‐metathesis reactions of terminal alkyl acetylenes with propynyl(trimethyl)silane to give products of type R¹?C?CSiMe . This unconventional way of introducing a silyl substituent onto an alkyne terminus complements the conventional tactics of deprotonation/silylation and excels as an orthogonal way of alkyne protecting group chemistry for substrates bearing base‐sensitive functionalities. Moreover, it is shown that even terminal aryl acetylenes can be cross‐metathesized with internal alkyne partners. These unprecedented transformations are compatible with various functional groups. The need to suppress acetylene formation, which seems to be a particularly effective catalyst poison, is also discussed.     

A Dicationic Ruthenium Alkylidene Complex for Continuous Biphasic Metathesis Using Monolith‐Supported Ionic Liquids

A dicationic ruthenium–alkylidene complex [Ru(dmf)₃(IMesH₂)(?CH‐2‐(2‐PrO)‐C₆H₄)][(BF₄)₂] ( 1 ; IMesH₂=1,3‐dimesitylimidazolin‐2‐ylidene) has been prepared and used in continuous metathesis reactions by exploiting supported ionic‐liquid phase (SILP) technology. For these purposes, ring‐opening metathesis polymerization (ROMP)‐derived monoliths were prepared from norborn‐2‐ene, tris(norborn‐5‐ene‐2‐ylmethyloxy)methylsilane, and [RuCl₂(PCy₃)₂(CHPh)] (Cy=cyclohexyl) in the presence of 2‐propanol and toluene and surface grafted with norborn‐5‐en‐2‐ylmethyl‐N,N,N‐trimethylammonium tetrafluoroborate ([NBE‐CH₂‐NMe₃][BF₄]). Subsequent immobilization of the ionic liquid (IL), 1‐butyl‐2,3‐dimethylimidazolium tetrafluoroborate ([BDMIM][BF₄]), containing ionic catalyst 1 created the SILP catalyst. The use of a second liquid transport phase, which contained the substrate and was immiscible with the IL, allowed continuous metathesis reactions to be realized. High turnover numbers (TONs) of up to 3700 obtained in organic solvents for the ring‐closing metathesis (RCM) of, for example, N,N‐diallyltrifluoroacetamide, diethyl diallylmalonate, diethyl di(methallyl)malonate, tert‐butyl‐N,N‐diallylcarbamate, N,N‐diallylacetamide, diphenyldiallylsilane, and 1,7‐octadiene, as well as in the self‐metathesis of methyl oleate, could be further increased by using biphasic conditions with [BDMIM][BF₄]/heptane. Under continuous SILP conditions, TONs up to 900 were observed. Due to the ionic character of the initiator, catalyst leaching into the transport phase was very low (<0.1 %). Finally, the IL can, together with decomposed catalyst, be removed from the monolithic support by flushing with methanol. Upon reloading with [BDMIM][BF₄]/ 1 , the recycled support material again qualified for utilization in continuous metathesis reactions.     

A Fast‐Initiating Ionically Tagged Ruthenium Complex: A Robust Supported Pre‐catalyst for Batch‐Process and Continuous‐Flow Olefin Metathesis

In this study, a new pyridinium‐tagged Ru complex was designed and anchored onto sulfonated silica, thereby forming a robust and highly active supported olefin‐metathesis pre‐catalyst for applications under batch and continuous‐flow conditions. The involvement of an oxazine–benzylidene ligand allowed the reactivity of the formed Ru pre‐catalyst to be efficiently controlled through both steric and electronic activation. The oxazine scaffold facilitated the introduction of the pyridinium tag, thereby affording the corresponding cationic pre‐catalyst in good yield. Excellent activities in ring‐closing (RCM), cross (CM), and enyne metathesis were observed with only 0.5 mol % loading of the pre‐catalyst. When this powerful pre‐catalyst was immobilized onto a silica‐based cationic‐exchange resin, a versatile catalytically active material for batch reactions was generated that also served as fixed‐bed material for flow reactors. This system could be reused at 1 mol % loading to afford metathesis products in high purity with very low ruthenium contamination under batch conditions (below 5 ppm). Scavenging procedures for both batch and flow processes were conducted, which led to a lowering of the ruthenium content to as little as one tenth of the original values.