N-Heterocyclic Carbenes in Late Transition Metal Catalysis

About Dendrimers: Structure, Physical Properties, and Applications

The increasing demand to produce enantiomerically pure pharmaceuticals, agrochemicals, flavors, and other fine chemicals has advanced the field of asymmetric catalytic technologies.1,2 Among all asymmetric catalytic methods, asymmetric hydrogenation utilizing molecular hydrogen to reduce prochiral olefins, ketones, and imines, have become one of the most efficient methods for constructing chiral compounds.3 The development of homogeneous asymmetric hydrogenation was initiated by Knowles4a and Horner4b in the late 1960s, after the discovery of Wilkinson’s homogeneous hydrogenation catalyst [RhCl(PPh3)3]. By replacing triphenylphosphine of the Wilkinson’s catalystwithresolvedchiralmonophosphines,6Knowles and Horner reported the earliest examples of enantioselective hydrogenation, albeit with poor enantioselectivity. Further exploration by Knowles with an improved monophosphine CAMP provided 88% ee in hydrogenation of dehydroamino acids.7 Later, two breakthroughs were made in asymmetric hydrogenation by Kagan and Knowles, respectively. Kagan reported the first bisphosphine ligand, DIOP, for Rhcatalyzed asymmetric hydrogenation.8 The successful application of DIOP resulted in several significant directions for ligand design in asymmetric hydrogenation. Chelating bisphosphorus ligands could lead to superior enantioselectivity compared to monodentate phosphines. Additionally, P-chiral phosphorus ligands were not necessary for achieving high enantioselectivity, and ligands with backbone chirality could also provide excellent ee’s in asymmetric hydrogenation. Furthermore, C2 symmetry was an important structural feature for developing new efficient chiral ligands. Kagan’s seminal work immediately led to the rapid development of chiral bisphosphorus ligands. Knowles made his significant discovery of a C2-symmetric chelating bisphosphine ligand, DIPAMP.9 Due to its high catalytic efficiency in Rh-catalyzed asymmetric hydrogenation of dehydroamino acids, DIPAMP was quickly employed in the industrial production of L-DOPA.10 The success of practical synthesis of L-DOPA via asymmetric hydrogenation constituted a milestone work and for this work Knowles was awarded the Nobel Prize in 2001.3k This work has enlightened chemists to realize * Corresponding author. 3029 Chem. Rev. 2003, 103, 3029−3069

New Chiral Phosphorus Ligands for Enantioselective Hydrogenation

The Golden Age of Transfer Hydrogenation

Recovery and reuse of expensive catalysts after catalytic reactions are important factors for sustainable process management. The aim of this Review is to highlight the progress in the formation and catalytic applications of magnetic nanoparticles and magnetic nanocomposites. Directed functionalization of the surfaces of nanosized magnetic materials is an elegant way to bridge the gap between heterogeneous and homogeneous catalysis. The introduction of magnetic nanoparticles in a variety of solid matrices allows the combination of well-known procedures for catalyst heterogenization with techniques for magnetic separation.

Magnetically Separable Nanocatalysts: Bridges between Homogeneous and Heterogeneous Catalysis

In this overview, recent trends and developments for the selective hydrogenation of multifunctional molecules are discussed and assessed from the point of view of fine chemicals synthesis. In a first part, the design and preparation of catalysts and ligands with interesting properties are summarized, particularly meant for the catalysis specialist. The following topics are described in some detail: How enantioselective homogeneous catalysts are designed and tested; new effective chiral monodentate phosphines; successful bidentate phosphines ligand families (with axially chiral biaryl- and ferrocenyl-based backbones, new phospholanes and with stereogenic phosphorus); novel bidentate ligand families with P-O and P-N bonds; and oxazoline-based ligands. A short overview on immobilized chiral complexes and of the toolbox of heterogeneous catalysis (bimetallic, colloidal and modified catalysts) concludes this chapter. In a second part, progress for selected catalytic transformations and generic selectivity problems is described, intended mainly for the organic chemist who has to solve specific synthetic problems. Emphasis is on the following topics: The enantioselective hydrogenation of olefins with various substitution patterns; the chemo- and enantioselective hydrogenation of ketones; the diastereo- and enantioselective hydrogenation of CN functions; the stereoselective hydrogenation of aromatic rings; chemoselectivity and hydroxylamine accumulation in the reduction of functionalized nitroarenes; chemoselectivity and new protecting groups for catalytic debenzylation; the mild hydrogenation of carboxylic acid derivatives; and the chemoselective hydrogenation of nitriles. In the last parts of the review, transfer hydrogenation and mechanistic issues are discussed, followed by a short conclusions and outlook paragraph.

Selective Hydrogenation for Fine Chemicals: Recent Trends and New Developments

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.

Solvias Josiphos Ligands: From Discovery to Technical Applications

In this overview, the opportunities and problems associated with the industrial application of chiral catalysts (restricted to homogeneous metal complexes and modified metallic catalysts) are being analyzed in detail. In a first chapter, critical factors affecting the industrial feasibility of an enantioselective catalyst are discussed. In the following chapters, chiral catalysts with synthetic relevance are described and about 40 types of catalytic transformations are discussed in some detail and characterized regarding enantioselectivity, catalyst activity and productivity. In addition, existing selected industrial applications for pharmaceuticals, agrochemicals and fragrances are reviewed. Finally the various transformations are assessed regarding their potential for future technical applications.

Progress in enantioselective catalysis assessed from an industrial point of view

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.

Benoit Pugin

Papers

Selective Hydrogenation for Fine Chemicals: Recent Trends and New Developments

Solvias Josiphos Ligands: From Discovery to Technical Applications

Progress in enantioselective catalysis assessed from an industrial point of view

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

Dendrimers Containing Chiral Ferrocenyl Diphosphine Ligands for Asymmetric Catalysis