Jeroen Wassenaar

Catalyst selection based on intermediate stability measured by mass spectrometry

The power of natural selection through survival of the fittest is natures ultimate tool for the improvement and advancement of species. To apply this concept in catalyst development is attractive and may lead to more rapid discoveries of new catalysts for the synthesis of relevant targets, such as pharmaceuticals. Recent advances in ligand synthesis using combinatorial methods have allowed the generation of a great diversity of catalysts. However, selection methods are few in number. We introduce a new selection method that focuses on the stability of catalytic intermediates measured by mass spectrometry. The stability of the intermediate relates inversely to the reactivity of the catalyst, which forms the basis of a catalyst-screening protocol in which less-abundant species represent the most-active catalysts, ‘the survival of the weakest’. We demonstrate this concept in the palladium-catalysed allylic alkylation reaction using diphosphine and IndolPhos ligands and support our results with high-level density functional theory calculations. Identifying the best catalyst for a particular reaction traditionally involves testing a wide variety of metal and ligand combinations in standard reactions. Here, the best catalyst is found by using mass spectrometry to identify the least stable — and thus most reactive — intermediate in a dynamic mixture of complexes.

Asymmetric Hydrogenation of Enamides, α-Enol and α-Enamido Ester Phosphonates Catalyzed by IndolPhos-Rh Complexes

The scope of the IndolPhos-Rh-catalyzed asymmetric hydrogenation of enamides, alpha-enol and alpha-enamido ester phosphonates, has been investigated. In addition, Taddol-based IndolPhos ligands are introduced. High activities and good to excellent enantioselectivities up to 99% ee are obtained for a broad range of structurally diverse substrates, giving important chiral products such as alpha, beta(2), and beta(3) amino acid derivatives, arylamines, and amino and hydroxy phosphonates.

Asymmetric Hydrogenation with Highly Active IndolPhos–Rh Catalysts: Kinetics and Reaction Mechanism

The mechanism of the IndolPhos-Rh-catalyzed asymmetric hydrogenation of prochiral olefins has been investigated by means of X-ray crystal structure determination, kinetic measurements, high-pressure NMR spectroscopy, and DFT calculations. The mechanistic study indicates that the reaction follows an unsaturate/dihydride mechanism according to Michaelis-Menten kinetics. A large value of K(M) (K(M) = 5.01+/-0.16 M) is obtained, which indicates that the Rh-solvate complex is the catalyst resting state, which has been observed by high-pressure NMR spectroscopy. DFT calculations on the substrate-catalyst complexes, which are undetectable by experimental means, suggest that the major substrate-catalyst complex leads to the product. Such a mechanism is in accordance with previous studies on the mechanism of asymmetric hydrogenation reactions with C(1)-symmetric heteroditopic and monodentate ligands.

Activation of H2 by a highly distorted RhII complex with a new C3-symmetric tripodal tetraphosphine ligand

Facile oxidation of a sterically encumbered Rh(I) complex generates a stable Rh(II) metalloradical species; the latter is able to activate H(2) under formation of the corresponding Rh(III) complex.

Versatile New C3-Symmetric Tripodal Tetraphosphine Ligands; Structural Flexibility to Stabilize CuI and RhI Species and Tune Their Reactivity

The high-yielding synthesis and detailed characterization of two well-defined, linkage isomeric tripodal, tetradentate all-phosphorus ligands 1-3 is described. Coordination to Cu(I) resulted in formation of complexes 4-6, for which the molecular structures indicate overall tridentate coordination to the copper atom in the solid state, with one dangling peripheral phosphine. The solution studies suggest fast exchange between the three phosphine side-arms. For these new Cu(I) complexes, preliminary catalytic activity in the cyclopropanation of styrene with ethyldiazoacetate (EDA) is disclosed. The anticipated well-defined tetradentate coordination in a C(3)-symmetric fashion was achieved with Rh(I) and Ir(I), leading to the overall five-coordinated complexes 7-12. Complex 11 has the norbornadiene (nbd) ligand coordinated in an unprecedented monodentate 2,3-eta(2) mode to Rh. Furthermore, unexpected but very interesting redox-chemistry and reactivity was displayed by the Rh(Cl)-complexes 7 and 8. Oxidation resulted in the formation of stable Rh(II) metalloradicals [7]PF(6) and [8]PF(6) that were characterized by X-ray crystallography, magnetic susceptibility measurements, cyclic voltammetry, and electron paramagnetic resonance (EPR) spectroscopy. Subsequent redox-reactivity of these metalloradicals toward molecular hydrogen is described, resulting in the formation of Rh(III) hydride compounds.

INDOLPhos: novel hybrid phosphine-phosphoramidite ligands for asymmetric hydrogenation and hydroformylation

Hybrid bidentate phosphine-phosphoramidite ligands are prepared in a modular 2-step sequence and their rhodium complexes display high selectivity in rhodium catalysed hydrogenation and hydroformylation reactions.