We report the template-induced formation of chelating heterobidentate ligands by the selective self-assembly of two different monodentate ligands on a rigid bis-zinc(II)-salphen template with two identical binding sites; these templated heterobidentate ligands induce much higher enantioselectivities (up to 72% ee) in the rhodium-catalyzed asymmetric hydroformylation of styrene than any of the corresponding homobidentate ligands or non-templated mixed ligand combinations (up to 13% ee).

Transition-metal-catalyzed asymmetric hydrogenation is one of the classic success stories in transition-metal catalysis because it has resulted in several scientific breakthroughs [1] as well as the development of commercial processes.[2] Many highly enantioselective catalysts for the asymmetric hydrogenation of various classes of prochiral substrates have been reported.[3] However, there are still many challenging substrates that cannot be converted with satisfactory enantioselectivities or yields, which has led to the ongoing intensive research efforts in this area. Although computational techniques are becoming increasingly important, one cannot design an enantioselective chiral catalyst in silico, and therefore, catalyst development for asymmetric reactions relies to a[*] Dr.

Combinatorial chemistry in combination with high‐throughput screening technologies is an important way of finding new successful catalyst systems. The design of ligand libraries of bidentate phosphorus ligands and the application of their transition‐metal complexes in homogeneous (asymmetric) catalysis reactions will be described in this review. Till now three different approaches were developed to arrive at such libraries of bidentate phosphorus ligands: 1) modular synthesis of bidentate ligands 2) the solid support synthesis of bidentate ligands and 3) the self‐assembly of ligand building blocks into bidentate ligands. The scope and limitations of these strategies will be discussed on the basis of a limited number of articles that dealt with the synthesis of at least 15 bidentate phosphorus ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The template-induced formation of chelating bidentate ligands by the selective self-assembly of two monodentate pyridyl phosphorus ligands on a rigid bis-zinc(II) salphen template with two identical binding sites was studied. Using UV-vis, NMR-spectroscopy and X-ray analysis the formed structures were unambiguously proven. The application of these templated bidentate ligands in transition metal catalysis showed, in most cases, typical bidentate character. Compared to previous work based on a more flexible bis-zinc(II) porphyrin template, the current catalytic data suggest that the rigidity of the template is not an important factor for the improvement of the regio-and enantioselectivity under the applied reaction conditions.The most powerful tool in homogeneous transition metal catalysis is ligand design and optimization. Various ligand parameters including steric properties, electronic properties, the bite angle and chirality, have shown to be important.1,2 Systematic variation of these properties is the general strategy for catalyst discovery and optimization. Traditionally, monodentate 3-6 and bidentate ligands 7,8 have been studied as important classes of ligands. For several reactions (hetero)bidentate ligands are superior compared to monodentate ligands, 2,9 but synthetic routes towards these ligands are generally more tedious.An important new strategy comprises a supramolecular approach to form (hetero)bidentate ligands. 10-19In this approach two monodentate ligands are brought together by a self-assembly process using non-covalent interactions such as hydrogen bonds, ionic or dynamic metal-ligand interactions. This class of ligands combines the advantages of synthetic accessibility and the selective formation of (hetero)bidentate ligands. Two monodentate ligands can be assembled by using ligands with complementary binding motifs, 11-14 or alternatively, a template can be used that contains binding sites for the assembly of two monodentate ligands.15 For example, we reported the use of a flexible bis-zinc(II) porphyrin template for the assembly of identical monodentate ligands, which led to chelating bidentate ligands that showed increased (enantio)selectivities in several reactions. tical binding sites (Fig. 1). 20 A more rigid template (i.e. the rigid bis-zinc(II) salphen versus the more flexible bis-zinc(II) porphyrin template used in previous studies) was anticipated to give rise to more selective catalyst systems. For the construction of templated self-assembled bidentate ligands we used two identical monomeric pyridyl phosphorus ligands. Transition metal complexes based on these templated bidentate ligands were explored in various catalytic transformations and they outperformed in most cases their non-templated analogues. Results and discussionWe studied the formation of templated bidentate ligand assemblies using monomeric pyridyl phosphorus ligands a-h in combination with a bis-zinc(II) salphen template 1 (Scheme 1). The bis-zinc(II) salphen building block was synthesized in a straightforward two...

The synthesis of a new series of diphosphine ligands based on 2,7-di-tert-butyl-9,9-dimethylxanthene (1), p-tolyl ether (2), ferrocene (3), and benzene (4) backbones, containing one or two 2,8-dimethylphenoxaphosphine moieties, is reported. The ligands were employed in the rhodium-catalyzed hydroformylation of 1-octene. For all four ligand backbones, introduction of phenoxaphosphine moieties led to an increase in catalytic activity and a decrease in regioselectivity toward the linear aldehyde product. Xanthene-based ligands 1a-1c yielded highly active and regioselective hydroformylation catalysts; ligands containing p-tolyl ether and ferrocene backbones 2a-2c and 3a-3c provided less active and less regioselective catalysts. Catalysts containing benzene-derived ligands 4a and 4b showed a remarkable preference for the formation of the branched aldehyde product. The coordination behavior of ligands 1-4 under hydroformylation conditions was investigated using high-pressure NMR and IR spectroscopy, revealing the distinct steric and electronic properties of the diphenylphosphine and 2,8-dimethylphenoxaphosphine moieties in ligands 1-4. The phosphacyclic moieties proved to be less basic and less sterically demanding toward other ligands in metal complexes than the acyclic diphenylphosphine moieties. For ligands that contain rigid backbones, the lack of conformational freedom in these phosphacyclic moieties does lead to repulsive interactions between the substituents of the two phosphorus donor atoms, resulting in an increase in the bite angle of the ligand. The low catalytic activity of rhodium catalysts modified by benzene-based ligands 4a-4c was attributed to the quantitative formation of HRh(L) 2 under hydroformylation conditions.