Hans-Ulrich Blaser

Selective Catalytic Hydrogenation of Functionalized Nitroarenes: An Update

In this update, progress made in the last decade for the selective catalytic hydrogenation of nitroarenes in the presence of other reducible functions is reviewed. The main focus is on catalytic systems capable of reducing nitro groups with very high chemoselectivity in substrates containing carbon–carbon or carbon–nitrogen double or triple bonds, carbonyl or benzyl groups, and multiple Cl, Br, or I substituents. The performance of new catalyst types is described, most notably of gold‐based catalysts, but also of modified classical Pt, Pd, and Ni catalysts, as well as homogeneous catalysts. The best results for the various chemoselectivity problems are compiled and assessed with regard to their versatility and synthetic viability. In addition, progress in understanding mechanistic aspects are briefly described.

Enantioselective hydrogenation of α-ketoesters using cinchona modified platinum catalysts and related systems: A review

Abstract The state of the art for the heterogeneous enantioselective hydrogenation of α-ketoesters using cinchona modified Pt catalysts and related systems is reviewed. The effect of the following elements of the catalytic system are well known: Catalyst. Supported Pt catalysts with relatively low dispersion (particle diameter >2 nm) are preferred for the hydrogenation of α-ketoacid derivatives, Pd catalysts for functionalized olefins. Most support materials are suitable. Substrate. The reacting function is preferentially a ketone or a C=C bond, a carbonyl group in a-position is necessary for good optical yields. Modifier. The minimal requirements for an efficient modifier for the hydrogenation of α-ketoesters is the presence of a basic nitrogen atom close to one or more stereogenic centers and connected to an extended aromatic system (preferentially quinolyl or naphthyl). The presence of an alcohol or ether in β-position to the basic nitrogen often gives better enantioselectivities. Solvent. Solvents with adielectric constant between 2 and 10 give best selectivities for a-ketoesters with best e.e.s in acetic acid. For the hydrogenation of substrates with a free acid function aqueous polar solvents are preferred. The highest optical yields for the different substrate types: 95% e.e. for α-ketoesters, 85% for a-ketoacids and 70% for α,)-unsaturated acids. Practical problems for the use of the catalytic system are low e.e.s at the start of the reaction, the instability of the modifier and some side reactions as well as the purity of the ethyl pyruvate. Mechanistic investigations have established interactions between substrate and modifier in solution and adsorption of the ethyl pyruvate and cinchonidine on the catalyst. The dependence of rate and e.e. on catalyst, cinchonidine, ethyl pyruvate and hydrogen concentration has been established for ethyl pyruvate hydrogenation using Pt/Al 2 O 3 -cinchona. A Langmuir-Hinshelwood scheme is well suited for explaining the observed kinetic results. Based on the kinetic results, the effect of modifier and substrate structure, and molecular modeling studies, the following mechanistic model has been developed: On the unmodified catalyst, the a-ketoester and hydrogen are reversibly adsorbed and the addition of the first hydrogen atom is rate determining. A modified active site is formed by adsorption of one cinchona molecule. It is postulated that a protonated adsorbed modifier interacts with the α-ketoester and forms a stabilized half hydrogenated intermediate. The rate determining step for the preferred enantiomer is the addition of the second hydrogen. The rate acceleration and the enantiodiscrimination is therefore due to the preferential stabilization of one of the two diastereomeric intermediates. Alternative mechanisms are discussed but considered to be less satisfying.

Supported palladium catalysts for fine chemicals synthesis

Abstract The contribution reviews the application of heterogeneous Pd catalysts for the manufacture of fine chemicals with special emphasis of their organic synthetic potential. In a first part, some background is given on the scope and limitations of homogeneous and heterogeneous catalysis and on significant parameters and the various types of supported Pd catalysts. Then, the application of supported Pd catalysts for important classes of transformations are reviewed organized according to reaction type. The general statements are illustrated with relevant examples from the literature and from our own laboratories. Hydrogenation, hydrogenolysis, and dehydrogenation reactions are considered to be mature technologies with an extremely broad scope both for small-scale laboratory applications and large to very large-scale manufacturing processes. Oxidation reactions and CC coupling reactions usually have a rather narrow scope and only relatively few have been developed to the technical stage. Especially for CC coupling reactions, the nature of the active Pd species is under debate because it is not clear whether the reaction takes place on the metallic surface or whether leached soluble Pd complexes are the active catalysts.

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 todays largest application of asymmetric catalysis and the Ir-xyliphos catalyst achieves unprecedented tons 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.

Solvias Josiphos ligands: from discovery to technical applications

The various stages from the invention of a ligand class to its technical application are described and illustrated by the case history of the Solvias Josiphos ligands. First, the prerequisites for a so-called “privileged ligand” are discussed, followed by a description of the Josiphos ligand family and their technical synthesis. Then, the catalytic performance of various Josiphos metal complexes in model reactions and in “real world” synthetic applications are summarized in the next two chapters. In the last part, three technical processes using Josiphos ligands are described: (i) The Ir-PPF-P(Xyl)2-catalyzed hydrogenation of MEA imine for the large scale production of the herbicide (S)-metolachlor; (ii) the application of a Rh-PPF-P(tBu)2 complex for the hydrogenation of a biotin intermediate; (iii) the Ru-PPF-P(Cy)2-catalyzed hydrogenation of a tetrasubstituted C=C bond for the production of cis-methyl dihydrojasmonate.

Enantioselective synthesis using chiral heterogeneous catalysts.

Abstract The application of solid chiral catalysts for the enantioselective synthesis of chiral molecules is reviewed. An attempt has been made to discuss critically the scope and limitations of these catalytic systems and their value for the synthetic organic chemist. The different catalytic systems described in the literature are tabulated and the enantioselectivities observed for different reactions are summarized according to the functional group which is transformed. Conclusions concerning synthetic and commercial-scale applications and some ideas on the mode of action of chiral solid catalysts are presented.

The palladium-catalysed arylation of activated alkenes with aroyl chlorides

Abstract Aroyl chlorides react with activated alkenes in presence of a tertiary amine and a catalytic amount of palladium acetate to give arylated alkenes, specifically cinnamic acid derivatives and stilbenes. The reaction involves a highly efficient decarbonylation of the aroyl chloride. High yields can be obtained at low catalyst concentration by choice of an appropriate base. The reaction is not particularly sensitive to substituents in the aroyl chloride, although strongly electron-donating groups are advantageous (yields up to 98%). With mono-substituted alkenes E -isomers are formed with almost complete specificity. A mechanism for the reaction is proposed.

More than 100,000 Turnovers with Immobilized Ir‐Diphosphine Catalysts in an Enantioselective Imine Hydrogenation

A modular concept to prepare immobilized enantioselective catalysts is described, consisting of a functionalized xyliphos ligand covalently attached to a support via a linker. Immobilized xyliphos bound to silica and to polystyrene as well as soluble dimeric xyliphos and an extractable analogue were prepared and tested in the Ir-catalyzed hydrogenation of a hindered N-arylimine used for the production of (S)-metolachlor. The best heterogeneous catalyst 9b exhibited TONs >100,000 and TOFs up to 20,000 h−1, the best values so far for immobilized catalysts. The immobilized catalysts gave similar enantioselectivities but lower activities and higher deactivation rates than the homogeneous analogues. These negative effects were tentatively explained by the higher local catalyst concentration on the support surface leading to an increased tendency to deactivation by irreversible dimer formation. Separation of these catalysts by filtration and extraction is easy and efficient.

Enantioselective Catalysis by Chiral Solids: Approaches and Results.

Abstract The application of solid chiral catalysts for the enantioselective synthesis of chiral molecules is reviewed. An attempt has been made to classify the different types of catalytic systems and to discuss the approaches and methods which have been used for the investigations. Enantioselectivities observed for several reaction types (hydrogenation/hydrogenolysis/dehydrogenation; electrochemical reactions; base catalysis; miscellaneous reactions) are summarized according to substrates and catalytic systems. The influence of system parameters and mechanistic investigations are reviewed for the following catalyst systems: Tartrate modified catalysts, cinchona modified catalysts and electrochemical systems. Conclusions concerning synthetic and commercial-scale applications of chiral solid catalysts are presented.

The role of catalysis for the clean production of fine chemicals

Abstract The role of catalysis for the production of fine chemicals is reviewed. The following topics are discussed on a general level: characteristics of the manufacture of fine chemicals, opportunities opened up by catalysis, critical factors for the application of catalysts and the tools that are available to the catalytic chemist. The general part is illustrated by specific examples from the catalysis group of Ciba-Geigy/Novartis such as chemoselective hydrogenations of aromatic nitro groups, the combination of a homogeneous and heterogeneous Pd catalyzed reaction for the alkylation of aromatic systems, catalytic systems for the enantioselective reduction of an α-keto ester, different routes to an N -alkylated hindered aniline including the (S)-metolachlor process, and the use of on-line monitoring of catalytic hydrogenations with ATR-probes. A short outlook on future developments is also presented.