Threonine‐Derived Phosphinite‐Oxazoline Ligands for the Ir‐Catalyzed Enantioselective Hydrogenation

A series of chiral phosphinite‐oxazolines was synthesized in four steps starting from carboxylic acids and threonine methyl ester. In the asymmetric hydrogenation of a number of alkenes, iridium complexes of these ligands induced significantly higher enantioselectivities than the corresponding serine‐derived complexes. Enantiomeric excesses of 89 to 99% were obtained for unfunctionalized alkenes with turnover numbers of up to 5000.     

Asymmetric Hydrogenation of Ketones with Polymer‐Bound BINAP/Diamine Ruthenium Catalysts

The BINAP/1,2‐diphenylethylenediamine RuCl₂ complexes bound to a polystyrene resin act as precatalysts for asymmetric hydrogenation of various simple ketones. The enantioselectivity, turnover number, and turnover frequency are comparable to those attained under homogeneous conditions.     

Heterogeneous Enantioselective Hydrogenation of Activated Ketones Catalyzed by Modified Pt‐Catalysts: A Systematic Structure‐Selectivity Study

A systematic structure‐selectivity study was carried out for the enantioselective hydrogenation of activated ketones with chirally modified Pt/Al₂O₃ catalysts. For this, 18 modifiers containing an extended aromatic system able to form a strong adsorption complex with the Pt surface, and a suitable chiral group with an amino function capable to interact with the keto group of the substrate ( HCd, Qd, HCn, Qn , and semi‐synthetic derivatives, as well as synthetic analogues) were prepared and tested on 8 different activated ketones in AcOH and toluene under standard conditions. It was found that relatively small structural changes of the substrate and/or modifier structures strongly affected the enantioselectivity, and that no “best” modifier exists for all substrates. The highest ees for all substrates were obtained with quinuclidine‐derived modifiers in combination with naphthalene or quinoline rings, either in AcOH (substrates 1 – 5 and 8 , all carrying an sp³ carbon next to the keto group) or toluene ( 6 and 7 , with an sp² carbon next to the ketone). The presence and nature of the substituent R' at the quinuclidine significantly affected the ee (positive and negative effects). Certain combinations of an aromatic system and an amino function were preferred: For the quinuclidine moiety, quinoline and to a somewhat lesser extent naphthalene were a better match, while for the pyrrolidinylmethyl group anthracene was better suited. Methylation of the OH group often had a positive effect for hydrogenations in AcOH but not in toluene. With the exception of 8 , higher ees were obtained for the Cd / Qn series [leading to (R)‐products] than for the Cn / Qd series [leading to (S)‐products]. In several cases, opposite structure‐selectivity trends were detected when comparing reactions in toluene and AcOH, indicating a significant influence of the solvent.     

The Chiral Switch of (S)‐Metolachlor: A Personal Account of an Industrial Odyssey in Asymmetric Catalysis

This account chronicles the various development phases of the Ir‐catalyzed enantioselective hydrogenation for the production of (S)‐metolachlor, the active ingredient of Dual Magnum^® (one of the most important grass herbicides for use in maize). The final process is today's largest application of asymmetric catalysis and the Ir‐xyliphos catalyst achieves unprecedented ton's of 2,000,000 and tof values around 600,000 h⁻¹. The development started in 1982 and ended when the first production batch was run in November 1996. On the one hand, the paper recounts the various breakthroughs and set‐backs and how the final catalytic system slowly evolved, and discusses on the other hand the strategies and approaches used for attaining the elusive goal. The various actions and decision points are analyzed and commented, and the roles and the seminal contributions of three key team members, Felix Spindler, Benoit Pugin, and Hans‐Peter Jalett are presented.     

Fluorinated Alcohols as Solvents for Enantioselective Hydrogenation with Chiral Self‐Assembling Rhodium Catalysts

We herein describe the beneficial effect of fluorinated alcohols on asymmetric hydrogenation using chiral self‐assembling rhodium complexes. Previously, the application of these catalysts has been hampered by low reaction rates in non‐polar solvents, which are essential for establishing the self‐assembling architecture via hydrogen bonding. Excellent reaction rates are usually observed in alcohols as solvents, but the characteristic hydrogen bonds are cleaved in those media, resulting in poor ee values. We now show for the first time that the disadvantageous properties of both solvent classes on the catalytic reaction can be overcome by using fluorinated alcohols. Due to this key finding, homogeneous catalysis with self‐assembling catalysts is much closer to practical application.     

New Silica‐Immobilized Nickel Catalysts for Cyclotrimerizations of Acetylenes

New dicarbonylnickel catalysts with a variety of mono‐ and bidentate phosphine ligands, such as Ph₂P(CH₂)_xPPh(CH₂)_ySi(OEt)₃ (x=2, 3; y=2, 3), have been synthesized and fully characterized, three of them by X‐ray analyses. All the catalysts have been immobilized on silica by reaction of the ethoxysilane or hydroxy groups of the phosphine linkers with the surface silanol groups. The clean immobilization was proved by ³¹P solid‐state NMR. It has been demonstrated that the C O Si bridge, in contrast to the strong Si O Si bond, is easily cleaved by organic solvents and water. With respect to the cyclotrimerization of phenylacetylene the optimal reaction conditions for all molecular and immobilized catalysts have been determined. Cyclooctane was the best solvent, and the optimal reaction temperature was 100 °C for reactions in homogeneous phase, and 155 °C for surface‐bound catalysts. The bite angles and spacer lengths of the chelating ligands did not play a major role for the performance of the homogeneous or immobilized catalysts. The latter could be recycled for 12 times, with final substrate conversions still typically between 30 and 40%, and turnover numbers (TON) around 1500. With an excess of substrate in one run a TON of 4810 was obtained for an immobilized carbonylnickel complex with a dppp‐type chelate phosphine (x=3, y=2). Reduction of the surface coverage generally resulted in catalysts with longer lifetimes, for example, reduction to one fourth gave a record TON of 7616 for this catalyst. The selectivities of the catalysts all followed one trend. The main products were the cyclotrimers 1,2,4‐ and 1,3,5‐triphenylbenzene, besides dimers, linear trimers and tetramers as side‐products. The fraction of the latter decreased at higher temperatures with homogeneous catalysts, and vanished entirely after a few cycles with the immobilized catalysts. On recycling, the initial ratio of unsymmetrical to symmetrical cyclotrimers of typically 5 : 1 gradually changed to about 1 : 1 for all catalysts.     

Ferrocenyl‐Aryl Based trans‐Chelating Diphosphine Ligands: Synthesis,Molecular Structure and Application in Enantioselective Hydrogenation

Potentially trans‐chelating diphosphine ligands based on a ferrocenyl‐aryl backbone were synthesised in a four‐step sequence and the molecular structures in the solid state of two representatives were determined by X‐ray diffraction. High throughput screening of these ligands in rhodium‐, ruthenium‐ and iridium‐mediated hydrogenations of a variety of alkenes and ketones revealed that these ligands can deliver high enantioselectivity for alkenes (up to 98% ee) but are less selective when ketones are used as the substrates. The coordination behaviour of one ligand in its square planar palladium and platinum dichloride complexes was studied by ³¹P NMR and only trans‐chelated complexes, together with oligomeric by‐products, were observed. Reaction with the (p‐cymene)ruthenium dichloride dimer, [RuCl₂(p‐cymene)]₂, resulted in a mixture of diastereomeric complexes.     

Enantioselective Hydrogenation of β‐Acylamino Acrylates Catalyzed by Rhodium(I)‐Monophosphite Complexes

Chiral rhodium(I) complexes bearing monophosphite ligands, prepared from chiral Binol and (L )‐menthol, were found to be efficient catalysts for the asymmetric hydrogenation of β‐acylamino acrylates with ee values up to 94%.     

A General Method for the Enantioselective Hydrogenation of β‐Keto Esters using Monodentate Binaphthophosphepine Ligands

17 monodentate phosphepine ligands with a 4,5‐dihydro‐3H‐dinaphtho[2,1‐c;1′,2′‐e]phosphepine structural motif have been synthesized and tested in the asymmetric hydrogenation of various β‐keto esters. By variation of the substituents of the aryl group on the phosphorus atom a fine tuning of the selectivity of the catalytic system is possible. Quantitative yield and enantioselectivities up to 95% ee have been achieved for the hydrogenation of methyl acetoacetate ( 7a ), methyl 3‐oxovalerate ( 7b ) and ethyl 4‐phenyl‐3‐oxo‐propionate ( 7d ) using 4‐(4‐methoxyphenyl)‐4,5‐dihydro‐3H‐dinaphtho‐[2,1‐c;1′,2′‐e]phosphepine ( 4g ) as ligand. Best enantioselectivities were obtained at comparably high temperatures (100–120 °C), which had the advantage of increased reaction rates.     

New Heterogenized Gold(I)‐Heterocyclic Carbene Complexes as Reusable Catalysts in Hydrogenation and Cross‐Coupling Reactions

Mononuclear unsymmetrical N‐heterocyclic carbene‐gold complexes and the corresponding solid catalysts in which a gold‐carbene complex has been immobilized on silica gel, ordered mesoporous silica (MCM‐41), and delaminated zeolite (ITQ‐2) have been prepared. These new catalysts have been tested in the hydrogenation of alkenes and the Suzuki cross‐coupling reaction to afford selectively non‐symmetrical biaryls. These reactions were studied with the soluble as well as with the heterogenized counterpart catalysts. The high accessibility introduced by the structure of the supports allows the preparation of highly efficient immobilized catalysts with TOFs up to 400 h⁻¹. Moreover, the heterogenized complexes were reused and no deactivation of the catalysts can be observed.     

Third‐Generation Amino Acid Furanoside‐Based Ligands from d‐Mannose for the Asymmetric Transfer Hydrogenation of Ketones: Catalysts with an Exceptionally Wide Substrate Scope

A modular ligand library of α‐amino acid hydroxyamides and thioamides was prepared from 10 different N‐tert‐butyloxycarbonyl‐protected α‐amino acids and three different amino alcohols derived from 2,3‐O‐isopropylidene‐α‐d ‐mannofuranoside. The ligand library was evaluated in the half‐sandwich ruthenium‐ and rhodium‐catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium‐hydroxyamide and the rhodium‐thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem α‐alkylation/asymmetric transfer hydrogenation of acetophenones and 3‐acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee.

     

Hydrogenation of Citral using Monometallic Pt and Bimetallic Pt‐Ru Catalysts on a Mesoporous Support in Supercritical Carbon Dioxide Medium

Supercritical carbon dioxide was shown to be a suitable reaction medium for the highly efficient hydrogenation of citral using monometallic Pt and bimetallic Pt‐Ru supported on a mesoporous material, MCM‐48, as catalyst. A remarkable change in the product distribution was observed after the addition of Ru to the monometallic Pt catalyst in supercritical carbon dioxide. The monometallic Pt catalyst was found to be highly selective to the unsaturated alcohol (geraniol+nerol) at a temperature of 323 K within 2 h whereas the bimetallic catalyst becomes selective to the partially saturated aldehyde (citronellal) under the same reaction conditions. Phase behavior plays an important role in the product distribution. Highest conversion and high selectivity to citronellal were achieved in the homogeneous phase for the Pt‐Ru catalyst while on the other hand the unsaturated alcohol (geraniol+nerol) was produced in the heterogeneous phase for the monometallic Pt catalyst. An XPS study offers strong evidence of the electronic modification of Pt after the addition of Ru in the bimetallic catalyst. The change in product distribution on the Pt‐Ru bimetallic catalyst may be explained by the appreciable interaction between the medium and the metal particles promoted by the presence of metallic Ru.     

Experimental and Kinetics Studies of Aromatic Hydrogenation in a Two‐Stage Hydrotreating Process using NiMo/Al2O3 and NiW/Al2O3 Catalysts

In this work, hydrogenation of aromatic compounds in light gas oil derived from Athabasca bitumen was carried out using a single‐ and two‐stage hydrotreating processes. Experiments were performed in a trickle‐bed reactor using two catalysts namely NiMo/Al₂O₃ and NiW/Al₂O₃. NiMo/Al₂O₃ was used in the first stage for nitrogen and sulphur containing heteroatoms removal whereas NiW/Al₂O₃ was used in the second stage for saturation of the aromatic rings in the hydrocarbon species. Temperature and liquid hourly space velocity (LHSV) were varied from 350‐390°C and 1.0‐1.5 h^?1, respectively, while pressure was maintained constant at 11.0 MPa for all experiments. Results from single‐stage were compared with those from two‐stage process on the basis of reaction time. Kinetic analysis of the single‐stage hydrotreating process showed that HDA and HDS activities were retarded by the presence of hydrogen sulphide that is produced as a by‐product of the HDS process. However, with inter‐stage removal of hydrogen sulphide in the two‐stage process, significant improvement of the HDA and HDS activities were observed.     

Mechanistic in situ High‐Pressure NMR Studies of Benzene Hydrogenation by Supramolecular Cluster Catalysis with [(η6‐C6H6)(η6‐C6Me6)2Ru3(μ3‐O)(μ2‐OH)(μ2‐H)2][BF4]

In situ high‐pressure NMR spectroscopy of the hydrogenation of benzene to give cyclohexane, catalysed by the cluster cation [(η⁶‐C₆H₆) (η⁶‐C₆Me₆)₂Ru₃(μ₃‐O)(μ₂‐OH)(μ₂‐H)₂]⁺ 2 , supports a mechanism involving a supramolecular host‐guest complex of the substrate molecule in the hydrophobic pocket of the intact cluster molecule.