Benoit Pugin

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.

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 imine hydrogenation with Ir diphosphine catalysts: fighting deactivation

Abstract While Ir diphosphine complexes are very active catalysts for the enantioselective hydrogenation of imines with good to excellent enantioselectivity, their deactivation is often a serious problem, leading to low catalyst productivity. Our study describes attempts to stabilize Ir catalysts with diop, bdpp and bppm ligands for the hydrogenation of different imines. The best results were obtained with complexes immobilised on silica gel and with bimetallic W–Ir and Mo–Ir complexes. In most cases, enantiomeric excesses as well as initial rates were only slightly affected while the stability of the catalysts was enhanced significantly.

Scope and Limitations of the Application of Heterogeneous Enantioselective Catalysts

The emphasis of this overview is placed on the synthetic potential and relevant characteristics of three classes of synthetic heterogeneous chiral catalysts (not covered are heterogeneous biocatalysts). i) Modified “classical” heterogeneous catalysts. The addition of chiral, low molecular weight modifiers to supported metal catalysts is most successful for preparing hydrogenation catalysts for α- and β-functionalized ketones. The main emphasis is on synthetic and technical applications but an update on mechanistic investigations and new systems is also given. The use of modified metal oxides is summarized. So far, only modified pillared clays for the epoxidation of allylic alcohols and the oxidation of aryl sulfides are of synthetic interest. ii) Chiral polymers. Reviewed are the uses of natural and synthetic chiral polymers as catalysts and supports. A few interesting concepts are described even though the synthetic application is restricted to poly(aminoacids) as selective catalysts for the epoxidation of chalcones and a polymer supported dipeptide for the hydrocyanation of aldehydes. A short section describes enantioselective reactions in chiral liquid crystal and gels. iii) Immobilized metal complexes. The preparation of different types of immobilized analogs of effective homogeneous chiral catalysts is assessed in detail. Each type is illustrated with representative examples. Requirements are discussed that are thought to be decisive for their synthetic application. Immobilized catalysts with high enantioselectivity and satisfactory activity have been developed for several reaction types. Most work has been carried out in hydrogenation, hydroformylation and oxidation reactions.

Enantioselective Metal Complex Catalysts Immobilized on Inorganic Supports Via Carbamate Links

Abstract Using O=C=N-(CH 2 ) 3 -Si(OEt) 3 as a linker, chiral diphosphine ligands containing an amine function were bound in a new and very efficient way to silicagel supports with different textures. The corresponding cationic rhodium complexes are very active catalysts for the enantioselective hydrogenation of methyl-acetamidecinnamate (ees up to 94.5%). They can easily be separated and successfully reused. Good catalysts with “molecular weights” as low as 5 kD can be obtained, since a high loading does not affect the catalytic performance, as long as the pores of the support are large.

Two enantioselective syntheses of a precursor of the biologically most active isomer of CGA 80000 (clozylacon)

Abstract The unchlorinated precursor 4 of CGA 80000 ( 1 ) was synthesized enantioselectively by two conceptionally different routes: a) by a “chiral pool” approach starting from L-malic acid and b) by enantioselective hydrogenation of an enamide intermediate, catalyzed by chiral Rh- or Ru-phosphine-complexes.

Enantioselective catalysis for agrochemicals: Synthetic routes to (S)-metolachlor, (R)-metalaxyl and (αS, 3R)-clozylacon

The application of enantioselective catalytic methods for the technical preparation of chiral agrochemicals is illustrated for three active ingredients of the acylanilide type. The key step for the technical synthesis of the herbicide (S)-metolachlor is the enantioselective hydrogenation of an imine intermediate using a novel iridium ferrocenyldiphosphine catalyst with an unprecedented high activity and 80% ee. (R)-metalaxyl and (αS,3R)-clozylacon were synthesized via the enantioselective hydrogenation of corre-sponding enamide precursors with Rh and Ru/binap catalysts with >95% and 99% enantiomeric purity, respectively.

Fengphos, a Ferrocene‐Based Chiral Diphosphine: Synthesis and Applications

New, effective chiral ligands are generally found by serendipity, since ab initio design is, to date, not possible. However, once a basic ligand structure is known to impart high selectivity to a catalyst, it is often possible to rationally design new variants on the basis of a structural hypothesis. Ever since the first highly selective diphosphines with a ferrocene backbone, such as bppfa and bppfOH (Figure 1) introduced by Kumada and