Looking Back on 35 Years of Industrial Catalysis.

This article is an account of my 35 years in the Basel Chemical Industry, starting in 1976 as a young research chemist in the Central Research Laboratories of Ciba-Geigy until my retirement as Chief Scientific Officer of Solvias in 2011. In the first section, important aspects of industrial research are commented from my personal point of view with particular emphasis on the importance of team work and the situation of catalysis in the (Swiss) fine chemicals industry. In the next sections, the three most important areas of catalytic research are described where my colleagues and I could not only solve specific Ciba-Geigy / Novartis / Solvias problems, but also developed industrially relevant, generally applicable catalytic methodologies and contributed to the understanding of these complex catalytic transformations: i) Catalytic C-C and C-N coupling catalysis where we developed highly efficient catalysts for the Heck, Suzuki, Buchwald-Hartwig reactions; ii) Hydrogenations using modified heterogeneous catalysts, especially the chemoselective reduction of functionalized nitro arenes and the enantioselective hydrogenation of substituted ketones using Pt catalysts modified with chinchona alkaloids where mechanistic studies led to a working understanding of this fascinating reaction; iii) Enantioselective homogeneous hydrogenation and chiral ligands. The process development for the production of (S)-metolachlor, an important herbicide via an iridium-Josiphos catalyzed C=N hydrogenation is described in some detail, followed by a brief description how the Solvias Ligand Portfolio was developed.

Looking Back on 35 Years of Industrial Catalysis.

This article is an account of my 35 years in the Basel Chemical Industry, starting in 1976 as a young research chemist in the Central Research Laboratories of Ciba-Geigy until my retirement as Chief Scientific Officer of Solvias in 2011. In the first section, important aspects of industrial research are commented from my personal point of view with particular emphasis on the importance of team work and the situation of catalysis in the (Swiss) fine chemicals industry. In the next sections, the three most important areas of catalytic research are described where my colleagues and I could not only solve specific Ciba-Geigy / Novartis / Solvias problems, but also developed industrially relevant, generally applicable catalytic methodologies and contributed to the understanding of these complex catalytic transformations: i) Catalytic C-C and C-N coupling catalysis where we developed highly efficient catalysts for the Heck, Suzuki, Buchwald-Hartwig reactions; ii) Hydrogenations using modified heterogeneous catalysts, especially the chemoselective reduction of functionalized nitro arenes and the enantioselective hydrogenation of substituted ketones using Pt catalysts modified with chinchona alkaloids where mechanistic studies led to a working understanding of this fascinating reaction; iii) Enantioselective homogeneous hydrogenation and chiral ligands. The process development for the production of (S)-metolachlor, an important herbicide via an iridium-Josiphos catalyzed C=N hydrogenation is described in some detail, followed by a brief description how the Solvias Ligand Portfolio was developed.

Developing catalysts and catalytic processes with industrial relevance.

The catalysis group of Solvias has its roots in the Central Research Laboratories of Ciba-Geigy. Since the early eighties its research has been focused on three areas of catalytic technology: heterogeneous hydrogenation, coupling catalysis, and enantioselective hydrogenation. Today, these are still the catalytic methods with the greatest industrial potential. In this overview a short description will be given how these methods have been developed further since the spin-off of Solvias in 1999. It will be discussed which strategies were successful and what the most important results have been in the first decade of Solvias.

Solphos: a new family of efficient biaryl diphosphine ligands.

Solphos (7,7'-bis(diarylphosphino)-3,3',4,4'-tetrahydro-4,4'-dimethyl-8,8'-bis-2H-1,4-benzoxazine) is a new modular atropisomeric biaryl ligand with a very attractive activity profile. A technically feasible synthesis is described allowing the synthesis of various derivatives of enantiopure ligand on a technical scale. Very good catalytic performances have been demonstrated for the following transformations: Ru-catalyzed hydrogenation of various beta-keto esters (95-99 % ee, s/c up to 100,000), of acetyl acetone (>99 % ee, dl/meso>98:2), and of an exocyclic alpha,beta-unsaturated acid (98.6 % ee, s/c 250). In several cases, the nature of the PAr(2) moiety had a significant effect on the enantioselectivity. Furthermore, Rh and Ir Solphos complexes achieved high enantioselectivities for a novel synthesis of 3,3-disubstituted phthalides and the reductive coupling of alkynes with N-sulfonyl imines, respectively.

From a chiral switch to a ligand portfolio for asymmetric catalysis.

This Account is divided into two sections. In the first section, the development of an enantioselective manufacturing process for ( S)-metolachlor, the active ingredient of the grass herbicide Dual Magnum, is described. This is today's largest application of asymmetric catalysis, and the Ir-Xyliphos hydrogenation catalyst achieves unprecedented 2 millions turnovers. The development started in 1982 and ended when the first production batch was run in November 1996. The strategies and approaches used for attaining the elusive goal are described, and the lessons learned are discussed. In the second section, the development and performance of a portfolio of chiral diphosphines for industrial asymmetric applications are described. Central to the portfolio is the idea of modular ligand families, i.e., diphosphines with the same backbone, where steric and electronic properties are easily tuned by the choice of the substituents at the phosphorous atoms.

Cinchona-modified platinum catalysts: from ligand acceleration to technical processes.

This Account records work carried out in our laboratories during the last 2 decades in the field of enantioselective heterogeneous hydrogenation. Of particular interest was Orito's catalytic system, platinum catalysts modified with cinchona alkaloids for the hydrogenation of activated ketones. Described are the development of the optimal platinum catalyst and modifier and the expansion of the scope of the catalyst. Kinetic studies aimed at understanding the mode of action of the catalyst revealed that the cinchona modifier not only renders the catalyst enantioselective but strongly accelerates the hydrogenation. This was the first case of ligand acceleration with a heterogeneous catalytic system. Finally, a number of industrial processes are summarized with the enantioselective hydrogenation of various alpha-keto esters as a key step.

No stirring necessary: parallel carbonylation of aryl halides with CO and various alcohols under pressure.

The parallel carbonylation of aryl halides with 6-25 bar of CO in 1-mL vials in a standard autoclave was investigated. 4-Bromoacetophenone and 2-chloropyridine were used as model substrates with 102 different O-nucleophiles (primary and secondary alcohols, phenols). No inertization during the loading was necessary. Fifty esters (43 new, yield up to 60%) were isolated and characterized. Ether, ester, ketone, and sometimes even olefin functions were usually tolerated. The new method is suitable for screening and small scale products synthesis.

Enantioselective catalysis in fine chemicals production.

The application of enantioselective catalysis to the fine chemicals industry has great potential both from economic and ecological points of view, but to date has not been widely implemented on a technical scale. The author hopes that the award of the 2001 Chemistry Nobel Prize in this field will give the necessary impetus to future applications.