Silica Immobilized Second Generation Hoveyda‐Grubbs: A Convenient,Recyclable and Storageable Heterogeneous Solid Catalyst

The second generation Hoveyda–Grubbs metathesis catalyst was successfully immobilized on silica in pellet and powder form following a practical and fast synthesis procedure. The activity of the solid system is truly heterogeneous, efficient in various metathesis reaction types and stable for at least 4000 TON. Ru contamination of the products was very low (ppb levels). The successful use of the robust system has been demonstrated in a continuous reactor set‐up.     

Asymmetric Homogeneous Hydrogenation in Flow using a Tube‐in‐Tube Reactor

In this update, the asymmetric homogeneous hydrogenation of a number of trisubstituted olefins utilizing the recently developed tube‐in‐tube gas‐liquid flow reactor is described. A number of chiral iridium‐ and rhodium‐based catalysts and other parameters such as pressure, solvent, temperature and catalyst loading were screened. The advantage of the flow set‐up for rapid screening and optimization of reaction parameters is illustrated. Furthermore, a comparative study using batch conditions aided in the optimization of the flow reaction set‐up. The set‐up was further modified to recycle the catalyst which prolonged catalytic activity.     

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.     

Thin Layer Chromatography for the Detection of Unexpected Reactions in Organometallic Combinatorial Catalysis

Thin layer chromatography (TLC) represents a fast and inexpensive alternative to NMR spectroscopy or analytical methods based on chromatography for the detection of unexpected products in organometallic combinatorial catalysis. This screening test led to the detection of the catalytic system [Ir(COD)Cl]₂/PPh₃ for isomerisation of diolefinic substrates instead the expected ring closing metathesis (RCM) reaction.     

Fast and Enantioselective Production of 1‐Aryl‐1‐propanols through a Single Pass,Continuous Flow Process

A functional polymer 4 , obtained by reaction of (R)‐2‐(1‐piperazinyl)‐1,1,2‐triphenylethanol with a Merrifield resin, has been loaded in a packed bed reactor and used as catalyst for the continuous enantioselective production of 1‐arylpropanols by ethylation of aromatic aldehydes. The high catalytic activity depicted by 4 allows the complete conversion of the substrates with the use of stoichiometric reagent ratios and unprecedently short residence times (down to 2.8 min). In practice, a single‐pass operation can be used for all the studied aldehydes, and productions of up to 13.0 mol/g h are recorded. The sequential operation of the flow system for the uninterrupted synthesis of a small library of enantiopure 1‐arylpropanols is also reported.     

Relay Catalysis: Enantioselective Synthesis of Cyclic Benzo‐Fused Homoallylic Alcohols by Chiral Brønsted Acid‐Catalyzed Allylboration/Ring Closing Metathesis

Six‐ and seven‐membered benzo‐fused cyclic homoallylic alcohols can be readily synthesized by a tandem chiral Brønsted acid‐catalyzed allyl (crotyl)boration/ring closing metathesis sequence performed under orthogonal relay catalysis conditions. Excellent enantio‐ and diastereoselectivities are obtained in most of the cases. In addition, the parent crotylboration/RCM process is also described. The required substrates, ortho‐vinylbenzaldehydes, are readily available in one step from commercially available starting materials. Both catalysts and reactants are also available from commercial suppliers. The reaction shows broad functional group compatibility and is also suitable for heteroaromatic substrates. Substitution at any position of the aromatic ring is tolerated; however, substitution at position 6 results in a substantial drop in enantioselectivity.     

Preparation of Optically Enriched 3‐Hydroxy‐3,4‐dihydroquinolin‐2(1H)‐ones by Heterogeneous Catalytic Cascade Reaction over Supported Platinum Catalyst

The development of a novel heterogeneous catalytic asymmetric cascade reaction for the synthesis of tetrahydroquinolines from 2‐nitrophenylpyruvates is reported. Optically enriched 3‐hydroxy‐3,4‐dihydroquinolin‐2(1H)‐ones are prepared by enantioselective hydrogenation of the activated keto group over a Cinchona alkaloid‐modified Pt catalyst, reduction of the nitro group and spontaneous cyclization cascade. Acceleration of the enantioselective hydrogenation of the activated keto group over the catalyst modified by Cinchona alkaloids ensured high tetrahydroquinolinone selectivities. The scope of the reaction was checked using twelve substrates. Both yields and enantioselectivities were significantly influenced by the nature and position of the substituents on the phenyl ring. Substituents adjacent to the nitro group considerably increased the product yield, due to their effect on the nitro group′s reduction rate; however, had only a limited effect on enantioselectivities.     

Monolith‐ and Silica‐Supported Carboxylate‐Based Grubbs–Herrmann‐Type Metathesis Catalysts

The synthesis of silica‐ and monolith‐supported Grubbs–Herrmann‐type catalysts is described. Two polymerizable, carboxylate‐containing ligands, exo, exo‐7‐oxanorborn‐2‐ene‐5,6‐dicarboxylic anhydride and 7‐oxanorborn‐2‐ene‐5‐carboxylic acid were surface‐immobilized onto silica‐ and ring‐opening metathesis (ROMP‐) derived monolithic supports using “grafting‐from” techniques. The “1^st generation Grubbs catalyst”, RuCl₂(CHPh)(PCy₃)₂, was used for these purposes. In addition, a poly(norborn‐2‐ene‐b‐exo, exo‐norborn‐2‐ene‐5,6‐dicarboxylic anhydride)‐coated silica 60 was prepared. The polymer supported anhydride and carboxylate groups were converted into the corresponding mono‐ and disilver salts, respectively, and reacted with the Grubbs–Herrmann catalyst RuCl₂(CHPh)(IMesH₂)(PCy₃) [IMesH₂=1,3‐bis(2,4,6‐trimethylphenyl)‐4,5‐dihydroimidazol‐2‐ylidene]. Heterogenization was accomplished by exchange of one chlorine ligand with the polymeric, immobilized silver carboxylates to yield monolith‐supported catalysts 4, 5 , and 6 as well as silica‐supported systems 7, 8 and 9 . The actual composition of these heterogenized catalysts was proven by the synthesis of a homogeneous analogue, RuCl[7‐oxanorbornan‐2‐(COOAg)‐3‐COO](CHPh)(IMesH₂)(PCy₃) ( 3 ). All homogeneous and heterogeneous catalysts were used in ring‐closing metathesis (RCM) of diethyl diallylmalonate, 1,7‐octadiene, diallyldiphenylsilane, methyl trans‐3‐pentenoate, diallyl ether, N,N‐diallyltrifluoracetamide and t‐butyl N,N‐diallylcarbamate allowing turnover numbers (TON's) close to 1000. In a flow‐through set‐up, an auxiliary effect of pendant silver carboxylates was observed with catalyst 5 , where the silver moiety functions as a (reversible) phosphine scavenger that both accelerates initiation and stabilizes the catalyst by preventing phosphine elution. Detailed catalytic studies were carried out with the monolith‐supported systems 4 and 6 in order to investigate the effects of temperature and chain‐transfer agents (CTA's) such as cis‐1,4‐diacetoxybut‐2‐ene. In all RCM experiments Ru‐leaching was low, resulting in a Ru‐content of the RCM products ≤3.5 μg/g (3.5 ppm).     

A Microfluidic Approach to the Rapid Screening of Palladium‐Catalysed Aminocarbonylation Reactions

The evaluation and selection of the most appropriate catalyst for a chemical transformation is an important process in many areas of synthetic chemistry. Conventional catalyst screening involving batch reactor systems can be both time‐consuming and expensive, resulting in a large number of individual chemical reactions. Continuous flow microfluidic reactors are increasingly viewed as a powerful alternative format for reacting and processing larger numbers of small‐scale reactions in a rapid, more controlled and safer fashion. In this study we demonstrate the use of a planar glass microfluidic reactor for performing the three‐component palladium‐catalysed aminocarbonylation reaction of iodobenzene, benzylamine and carbon monoxide to form N‐benzylbenzamide, and screen a series of palladium catalysts over a range of temperatures. N‐Benzylbenzamide product yields for this reaction were found to be highly dependent on the nature of the catalyst and reaction temperature. The majority of catalysts gave good to high yields under typical flow conditions at high temperatures (150 °C), however the palladium(II) chloride‐Xantphos complex [PdCl₂(Xantphos)] proved to be far superior as a catalyst at lower temperatures (75–120 °C). The utilised method was found to be an efficent and reliable way for screening a large number of palladium‐catalysed carbonylation reactions and may prove useful in screening other gas/liquid phase reactions.     

High-throughput preparation and screening of rhenium oxide-alumina catalysts in olefin metathesis

High-throughput (HT) experimentation in heterogeneous catalysis exemplifies a multidisciplinary approach to address in an efficient manner different aspects of catalyst development – from synthesis to testing and characterization. The present work reports on preparation systems for rapid parallel synthesis of well defined heterogeneous catalysts and catalyst screening in olefin metathesis. Metathesis of ethene and but-2-ene to propene was chosen as a test reaction. The influences of various parameters such as rhenium oxide loading, catalyst calcination conditions, catalyst pre-treatment, as well as the reaction temperature and contact time on the catalytic performance are discussed. Sample characterization by UV–vis and FT-IR gave an evidence for the formation of active surface perrhenate species, very sensitive to humidity and pre-treatment conditions applied.     

Ferrocene Redox Controlled Reversible Immobilization of Ruthenium Carbene in Ionic Liquid: A Versatile Catalyst for Ring‐Closing Metathesis

A ferrocene‐tagged ruthenium carbene 15 that can be reversibly immobilized in an ionic liquid (IL) via the controlled oxidation and reduction of a ferrocene tag was prepared. This offers a new strategy which uses redox chemistry to control immobilization and to recycle both the catalyst and the IL. In this experiment, 11 recycles were performed for the ring‐closing metathesis (RCM) of a substrate using 16 as the catalyst in an ionic liquid (IL). More importantly, after the reaction was completed, the ruthenium catalyst was easily separated from the supporting IL by just adding decamethylferrocene (DMFc) to reduce the cationic ferrocene and then extracting it with benzene. Thus, this recycle system offers an easy way to recycle both the ruthenium catalyst and the IL.     

Bismuth Triflate‐Catalyzed Addition of Allylsilanes to N‐Alkoxycarbonylamino Sulfones: Convenient Access to 3‐Cbz‐Protected Cyclohexenylamines

Bismuth triflate was found to be an efficient catalyst in the Sakurai reaction of allyltrimethylsilanes with N‐alkoxycarbonylamino sulfones. The reaction proceeded smoothly with a low catalyst loading of Bi(OTf)₃⋅4 H₂O (2–5 mol%) to afford the corresponding protected homoallylic amines in very good yields (up to 96%). A sequential allylation reaction followed by ring‐closing metathesis delivers 6–8 membered 3‐Cbz‐protected cycloalkenylamines.     

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.

     

Catalytic dehydration of glucose to 5‐hydroxymethylfurfural with a bifunctional metal‐organic framework

Glucose conversion to 5‐hydroxymethylfurfural (HMF) generally undergoes catalytic isomerization reaction by Lewis acids followed by the catalytical dehydration to HMF with Brönsted acid. In this work, a sulfonic acid functionalized metal‐organic framework MIL‐101(Cr)‐SO₃H containing both Lewis acid and Brönsted acid sites, was examined as the catalyst for γ‐valerolactone‐mediated cascade reaction of glucose dehydration into HMF. Under the optimal reaction conditions, the batch heterogeneous reaction gave a HMF yield of 44.9% and selectivity of 45.8%. Reaction kinetics suggested that the glucose isomerization in GVL with 10 wt % water follows the second‐order kinetics with an apparent activation energy of 100.9 kJ mol^?1. Continuous reaction in the fixed‐bed reactor showed that the catalyst is highly stable and able to provide a steady HMF yield. This work presents a sustainable and green process for catalytic dehydration of biomass‐derived carbohydrate to HMF with a bifunctional metal‐organic framework. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4403–4417, 2016     

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.     

Siliceous Mesocellular Foam‐Supported Aza(bisoxazoline)‐Copper Catalysts

Aza(bisoxazoline) was easily immobilized on siliceous mesocellular foam (MCF) in a systematic approach. It was found that silanol precapping, linker group flexibility, ligand loading, and silanol postcapping were important factors to consider in optimizing silica‐supported aza(bisoxazoline) catalysts. The optimized MCF‐supported aza(bisoxazoline)‐copper catalyst offered the same enantioselectivity as its homogeneous counterpart, and excellent recyclability. The heterogenized catalyst showed a much higher chemoselectivity in a short reaction time. The heterogenized aza(bisoxazoline)‐copper(I) catalyst was successfully applied to a circulating flow‐type packed bed reactor with excellent productivity and enantioselectivity. The circulating flow‐type reactor was found to be very useful for gas‐generating catalytic reactions such as cyclopropanation reaction.     

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.     

Hybrid‐Bridged Silsesquioxane as Recyclable Metathesis Catalyst Derived from a Bis‐Silylated Hoveyda‐Type Ligand

The synthesis of a bis‐silylated Hoveyda‐type monomer is described as well as the preparation of several organic‐inorganic hybrid materials derived from it by a sol‐gel process (with and without tetraethyl orthosilicate) and by anchoring to MCM‐41. The resulting materials were treated with second generation Grubbs' catalyst to generate second generation Hoveyda–Grubbs‐type alkylideneruthenium complexes covalently bonded to the silica matrix. These materials are recyclable catalysts for the ring‐closing metathesis reaction of dienes and enynes.     

Application of a Homogeneous Dodecakis(NCN‐PdII) Catalyst in a Nanofiltration Membrane Reactor under Continuous Reaction Conditions

A shape‐persistent nanosize dodecakis(NCN‐Pd^II‐aqua) complex ( 4b ) was applied as a homogeneous catalyst in the double Michael reaction between methyl vinyl ketone and ethyl α‐cyanoacetate under continuous reaction conditions in a nanofiltration membrane reactor. Due to its macromolecular dimensions, the catalyst is retained in the reactor (R=99.5% determined by ICP‐AAS) during catalysis. In addition, the catalyst was found to be stable under the continuous reaction conditions as a constant activity was obtained at prolonged reaction times (26 h, 65 exchanged reactor volumes). The turnover number of the catalyst was thus increased by a factor greater than 40 from 80 (batch) up to >3000 mol/mol Pd. Further development of this technology will allow an increase of the number of (industrial) catalytic processes in which homogeneous catalysts are applied.     

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.