New Indenylidene‐Schiff Base‐Ruthenium Complexes for Cross‐Metathesis and Ring‐Closing Metathesis

We here report on the stability and catalytic activity of new indenylidene‐Schiff base‐ruthenium complexes 3a – f through representative cross‐metathesis (CM) and ring‐closing metathesis (RCM) reactions. Excellent activity of the new complexes was found for the two selected RCM reactions; prominent conversion was obtained compared to the commercial Hoveyda–Grubbs catalyst 2 . Moreover, excellent results were obtained for a standard CM reaction. Higher conversions were achieved with one of the indenylidene catalysts compared with Hoveyda–Grubbs catalyst. Unexpectedly, an isomerization reaction was observed during the CM reaction of allylbenzene. To the best of our knowledge, isomerization reactions in this model CM reaction in closed systems have never been described using first generation catalysts, including the Hoveyda–Grubbs catalyst. The first model CM reactions as well as the RCM reactions have been monitored using ¹H NMR. The course of the CM reaction of 3‐phenylprop‐1‐ene ( 8 ) and cis‐1,4‐diacetoxybut‐2‐ene ( 9 ) was monitored by GC. The isomerization reaction was studied by means of GC‐mass spectrometry and in situ IR spectroscopy. All catalysts were structurally characterized by means of ¹H, ¹³C, and ³¹P NMR spectroscopy.     

Optimization of Ring‐Closing Metathesis: Inert Gas Sparging and Microwave Irradiation

A systematic study of a ring‐closing metathesis towards a tetrasubstituted double bond as part of a seven‐membered ring in a 5.7.5‐tricyclic guaianolide system is described. By combining two techniques, namely sparging an inert gas through the solution together with dielectric heating via microwave irradiation a high‐yielding ring‐closing metathesis reaction in this particularly challenging case was achieved. The results obtained compare favorably with conventional heating conditions or with microwave irradiation in a closed system. The key aspects seem to be that rapid microwave irradiation diminishes catalyst decay by allowing the required high reaction temperature to be reached quickly and homogeneously and thereby providing enough energy for a successful metathesis reaction, while inert gas sparging is purging off evolving ethylene to shift the equilibrium to the product.     

Ring Size‐Selective Ring‐Closing Olefin Metathesis: Taking Advantage of the Deleterious Effect of Ethylene Gas

The deleterious effect of ethylene gas on the ring‐closing olefin metathesis (RCM) for the formation of 5‐ to 8‐membered rings was investigated. Significant rate differences caused by ethylene gas were observed among the different ring‐size formation reactions. Nevertheless, the rate differences can be advantageously utilized for chemoselective RCM.     

A Highly Active and Reusable Heterogeneous Ruthenium Catalyst for Olefin Metathesis

The synthesis and characterization of Ru complexes of the type [L₂X₂RuCHR] (L=PPh₃, PCy₃, N‐heterocyclic carbenes or their derivates; X=Cl) grafted on mesoporous SBA‐15 material are described. In this heterogeneous catalyst the Ru complexes are anchored in the pore channels of mesoporous silica material SBA‐15 to prevent the decomposition of the catalytic species. Compared with formal organic‐supported heterogeneous catalysts, this heterogeneous catalyst shows relatively high catalytic activity in olefin metathesis reactions and can be used several times without any decrease in catalytic activities.     

Unexpected Results of a Turnover Number (TON) Study Utilising Ruthenium‐Based Olefin Metathesis Catalysts

A turnover number (TON) study of ruthenium‐based metathesis catalysts has been conducted for ring‐closing metathesis (RCM) in dilute solution. Unexpectedly the results indicate that 1^st generation metathesis catalysts can give higher TON in RCM of simple unsubstituted terminal olefins than their second generation counterparts. In particular, the 1^st generation Hoveyda–Grubbs catalyst showed unexpectedly high activity, particularly when compared to the 2^nd generation catalysts.     

Mesocellular Foam‐Supported Catalysts: Enhanced Activity and Recyclability for Ring‐Closing Metathesis

Although ring‐closing metathesis (RCM) has been one of the most powerful methodologies for creating cyclic compounds, the pharmaceutical industry has not yet widely adopted this process commercially due to the high costs and leaching problems of homogeneous ruthenium catalysts. To circumvent these problems, we have immobilized the second‐generation Hoveyda–Grubbs catalyst effectively onto siliceous mesocellular foam (MCF). The open and interconnected pores of MCF facilitated ligand immobilization and substrate diffusion. We have observed that the ligand and metal loadings significantly affected the catalytic activity and recyclability. Enhanced recyclability by suppression of ruthenium leaching was achieved by using excess immobilized ligands. The resulting novel heterogenized catalysts demonstrated excellent activity and reusability for the RCM of various types of substrates.     

A Ruthenium Catalyst for Olefin Metathesis Featuring an Anti‐Bredt N‐Heterocyclic Carbene Ligand

A ruthenium complex bearing an “anti‐Bredt” N‐heterocyclic carbene was synthesized, characterized and evaluated as a catalyst for olefin metathesis. Good conversions were observed at room temperature for the formation of di‐ and tri‐substituted olefins by ring‐closing metathesis. It also allowed for the ring‐opening metathesis polymerization of cyclooctadiene, as well as for the cross‐metathesis of cis‐1,4‐diacetoxy‐2‐butene with allylbenzene, with enhanced Z/E kinetic selectivity over classical NHC‐based catalysts.

     

Iridium‐Catalyzed Asymmetric Allylic Etherification and Ring‐Closing Metathesis Reaction for Enantioselective Synthesis of Chromene and 2,5‐Dihydrobenzo[b]oxepine Derivatives

Iridium‐catalyzed asymmetric etherifications of allylic carbonates with 2‐vinylphenols and 2‐allylphenols were realized. With a catalyst generated from 2 mol% of [Ir(cod)Cl]₂ (cod=cycloocta‐1,5‐diene) and 4 mol% of the phosphoramidite ligand L2 , the etherification products were obtained in excellent ees and then subjected to the ring‐closing metathesis reaction providing an efficient synthesis of enantioenriched 2H‐chromene and 2,5‐dihydrobenzo[b]oxepine derivatives.     

Progress towards the Stereoselective Synthesis of 3,6‐Disubstituted 1,2‐Diamino‐4‐cyclohexenes by Ring Closing Metathesis Reaction

The ring closing metathesis of 4(R),5(R)‐bis[1(S)‐phenylethylamino]‐3,6‐diethenyl‐1,7‐octadiene required the preliminary formation of the cyclic formaldehyde aminal, then the use of the Grubbs' ruthenium benzylidene complex (10 mol %) in refluxing toluene in the presence of 2 equivalents of trifluoroacetic acid. The cyclic aminal was cleaved in situ after the cyclisation step, so that the final product was the 1,2‐diamino‐3,6‐diethenylcyclohex‐4‐ene derivative. The predominant C₁‐symmetric diastereomer was isolated with 48% yield.     

Synthesis of Pyrrolizidine,Indolizidine, and Quinolizidine Derivatives Using Ruthenium‐Catalyzed Ring‐Opening Metathesis and Ring‐Closing Metathesis of Cycloalkene‐ynes

Ring‐opening metathesis and ring‐closing metathesis (ROM‐RCM) of a cyclopentene‐yne having an ester moiety was demonstrated using first‐ and second‐generation Grubbs’ catalysts. When the reaction of cycloalkene‐yne was carried out in the presence of 5 mol % of a ruthenium carbene complex under an ethylene atmosphere at room temperature, ROM‐RCM proceeded smoothly to give a pyrrolidine derivative in good yield, which could be converted to a pyrrolizidine derivative. Furthermore, ROM‐RCM of azabicyclo[2.2.1]heptene‐ynes using the second‐generation Grubbs’ catalyst was investigated. When an azabicycloheptene derivative was exposed to a catalytic amount of a ruthenium carbene complex, pyrrolizidine and indolizidine derivatives were obtained in good yields. The distribution of these products depends on the substituents on the alkyne. When azabicyclo[2.2.1]heptene‐ynes bearing large substituents on the alkyne were treated with ruthenium catalyst 1b , a pyrrolizidine derivative was obtained as the major product. ROM‐RCM of azabicyclo[2.2.2]octene‐ynes with 1b afforded quinolizidine derivative 20 , although the yield was moderate.     

Formation of Arenes via Diallylarenes: Strategic Utilization of Suzuki–Miyaura Cross‐Coupling,Claisen Rearrangement and Ring‐Closing Metathesis

Two new synthetic strategies for benzoannulation are reported. The first strategy is based on the Suzuki–Miyaura cross‐coupling reaction. To this end, various ortho‐diallylbenzene derivatives were prepared from the corrresponding diiodo derivatives by an allylation strategy using an allylboronate as coupling partner. These diallyl derivatives were subjected to a ring‐closing metathesis (RCM) and one‐pot dichlorodicyanoquinone (DDQ) oxidation sequence to deliver 2‐substituted naphthalenes. In the second strategy, a double Claisen rearrangement and RCM protocol have been used as key steps to give highly functionalized benzoannulated quinone derivatives.     

Polymer‐Supported Indium Lewis Acid: Highly Versatile Catalyst for Regio‐ and Stereoselective Ring‐Opening of Epoxides

The first example of a polymer‐supported indium Lewis acid is presented. This new heterogeneous Amberlyst 15/indium complex effectively catalyses (20 mol % based on indium) the formation of new C C as well as C S bonds through the highly regio‐ and stereoselective ring‐opening reaction of enantiomerically pure epoxides. The easily prepared Amberlyst 15/indium Lewis acid does not require inert atmosphere conditions or anhydrous media and can be easily recovered and recycled for several times without loss of activity.     

Olefin Metathesis of Vinylgermanium Derivatives as Method for the Synthesis of Functionalized Cubic and Double‐Decker Germasilsesquioxanes

For the first time, olefin cross metathesis has been developed for vinylgermanium compounds. This paper also marks the first case of transition metal‐catalyzed functionalization of heterosilsesquioxanes, which in our case are cubic vinylgermasilsesquioxanes and newly synthesized di(vinylgermyl)substituted double‐decker silsesquioxane. These processes lead to a series of new molecular, unsaturated mono‐ and divinyl‐substituted germasilsesquioxanes, which can be potentially applied as precursors for optoelectronics and for the synthesis of new advanced materials. Additionally, preliminary tests of metathetic copolymerization of divinylsubstituted double‐decker digermasilsesquioxanes (DDSQ‐2ViGe) with selected diolefins proved to be very promising and resulted in the synthesis of novel stereoregular trans‐germasilsesquioxyl‐vinylene‐phenylene macromolecular derivatives. All newly obtained compounds were isolated and characterized by mass and spectroscopic methods.

     

Olefin Metathesis on a TLC Plate as a Tool for a High‐Throughput Screening of Catalyst‐Substrate Sets

A methodology for screening either various catalysts for a given metathesis reaction, i.e., ring opening‐ring closing alkene metathesis (RO‐RCM) and cross‐metathesis (CM), or various substrates for a given pre‐catalyst on a thin layer chromatography (TLC) plate has been developed. As the substrates elute with the solvent, this TLC‐based system acts as a heterogeneous catalyst bed (“TLC reactor”). Selected promising catalyst candidates were screened on a TLC plate and their initial catalytic potential as observed in the TLC test was later fully confirmed in a classical heterogeneous reaction set‐up using standard commercially available silica (D11‐10). Reacting polyfunctional, natural product‐like substrates in our TLC reactor allows the simultaneous screening of various substrates and the convenient micro‐scale preparation and isolation of potentially biologically active products.     

Direct and Transfer Hydrogenation of Ketones and Imines with a Ruthenium N‐Heterocyclic Carbene Complex

The dihydride ruthenium N‐heterocyclic carbene complex Ru(IMes)(PPh₃)₂CO(H)₂ ( 1 ) (IMes=1,3‐dimesityl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene) is an efficient catalyst for both direct hydrogenation and transfer hydrogenation of ketones and imines, in the absence of base.     

(−)‐Sparteine‐Mediated Directed ortho‐Metalation of N‐Cumyl‐N‐ethylferrocenecarboxamide. Versatile Routes to Functionalized Planar Chiral Ferrocenecarboxamides,Amines, Esters and Phosphines

N‐Cumyl‐N‐ethylferrocenecarboxamide 5 provides planar chiral carboxamides 6 in high yield and % ee via (−)‐sparteine‐mediated directed ortho‐metalation. Mild decumylation affords secondary amides 7 , which serve as intermediates for a convenient and general route to the venerable Ugi planar chiral ferrocenylamines 13 and as versatile precursors for the preparation of novel chiral ferrocenes 15 and 20 . The chiral TMS‐ferrocenyl derivative 7c is used to prepare the enantiomeric (S)‐ 7f , circumventing the lack of availability of (+)‐sparteine.     

Controlled Reversible Anchoring of η6‐Arene/TsDPEN‐ Ruthenium(II) Complex onto Magnetic Nanoparticles: A New Strategy for Catalyst Separation and Recycling

A new catalyst separation and recycling protocol combining magnetic nanoparticles and host‐guest assembly was developed. The catalyst, (η⁶‐arene)[N‐(para‐toluenesulfonyl)‐1,2‐diphenylethylenediamine]ruthenium trifluoromethanesulfonate [Ru(OTf)(TsDPEN)(η⁶‐arene)] bearing a dialkylammonium salt tag, was easily separated from the reaction mixtures by magnet‐assisted decantation, on basis of the formation of a pseudorotaxane complex by using dibenzo[24]crown‐8‐modified Fe₃O₄ nanoparticles. The ruthenium catalyst has been successfully reused at least 5 times with the retention of enantioselectivity but at the expense of relatively low catalytic activities in the asymmetric hydrogenation of 2‐methylquinoline.     

Low Catalyst Loadings in Self‐Metathesis of 1‐Dodecene

A series of ruthenium catalysts has been screened in the self‐metathesis of 1‐dodecene with and without the addition of benzoquinones. Many of these catalysts demonstrated excellent selectivity and yields with as low as 10 ppm catalyst loading. Reactions have been conducted under decreased pressure or under argon bubbling, which caused a tremendous increase in yield and selectivity of the examined process.     

An Immobilised Grubbs 2nd Generation Catalyst for Application in Flow‐Through Devices

An improved immobilised Grubbs 2^nd generation catalyst and its application in flow‐through devices, shown for on‐column reaction gas chromatography (ocRGC), has been studied. The coupling of a reaction capillary and a separation column in GC/MS allows direct reaction monitoring and analysis of conversion as well as reaction kinetics. The presented permanently bonded N‐heterocyclic carbene ligand shows a great stability and activity in ring closing metathesis reactions. A salt‐free approach was used to generate the carbene ligand, which can be directly monitored by mass spectrometry. The very flexible design of the immobilised ligand system in reaction channels and capillaries of flow through systems allows the preparation of various catalysts using a broad variety of metal precursors. This strategy of immobilised catalytically active complexes offers a wide range of on‐column reactions combinable with fast reaction screening by high throughput experimentation.