Polydentate Chiral Ligands with Phosphorus-Nitrogen Co-ordination Sites and Their Use in Asymmetric Catalysis

Several groups of structurally related ligands have been synthesized and used as chiral auxiliaries in palladium catalyzed asymmetric carbon-carbon bond forming reactions. Using DFT and molecular mechanics calculations it was possible to identify the type of interactions between substrate and ligand which are responsible for different degrees of selectivity observed in the experiments. One of the typical challenges in modern synthetic chemistry is to develop methods for a selective and economic access to new products. Most of the more complex chemical structures do exist in two isomeric forms which are not superimposible but are related as an image and its mirror image. These are called enantiomers. Typical synthetic procedures afford such products as a 1:1 mixture of the enantiomers. Enantiomers do have identical physical properties and cannot be separated from each other by common separation techniques. If, at the other hand, these enantiomers interact with one enantiomeric form of another compound they behave differently. Since all organisms are formed from enantiomerically pure molecules it is expected that also enantiomeric forms of bioactive compounds used in medicine will cause a different response from the human organism. This is an unacceptable situation since unpredictable and undesired reactions may occur and consequently it is nowadays unlawful to employ drugs which are not enantiomerically pure. This explains the high importance of asymmetric synthetic methods yielding to pure enantiomers. Particularly procedures utilizing optically active catalysts (asymmetric or enantioselective catalysis) have become a field of intensive research in organic and especially metal organic chemistry. The principle is simple: One enantiomeric form of a chiral auxiliary is bound to a catalytically active transition metal to form a catalyst which favors the formation of only one product enantiomer. Since the catalyst is not consumed during the reaction, in theory a single molecule is sufficient to produce an indefinite amount of (in an ideal case) enantiomerically pure product. A central role will play the proper choice of the ligand to obtain catalysts with high selectivity and reactivity. In general a high substrate specificity is observed, in other words, different substrates require different ligands. The synthetic path to the ligands should therefore designed in a way to enable structural variations, in order to get an optimal fit of ligand and substrate (key-lock interaction). In this research project several groups of new ligands have been synthesized and applied in palladium mediated carbon-carbon bond forming reactions. In a number of cases excellent enantioselectivities have been observed. With the aim of spectroscopic methods and after isolation of intermediates and determination of their crystal structure it was possible to identify key intermediates. Ab initio and molecular mechanics calculation methods applied to these species elucidated areas of positive and negative interaction between substrate and ligand and enabled a rational explanation of experimentally observed selectivities.