Oxazoline based transition metal catalysts for asymmetric transformations

For the production of bioactive compounds such as drugs, fragrances, herbicides or pesticides more and more selective and environmentally benign synthesis methods are required. Since many of these derivatives can exist in two mirror image like forms which usually show different biological activity highly selective synthesis methods are an absolute necessity. Homogeneous asymmetric catalysis constitutes one very powerful methodology for the synthesis of such so called enantiopure derivatives. Besides enzymes, transition metal complexes have been used most successfully as asymmetric catalysts. For large scale industrial reactions especially asymmetric hydrogenations are of prime interest since in these reactions cheap hydrogen gas is used as the reagent and almost no reaction waste is formed. In most cases, hydrogenation catalysts are coordination compounds of either ruthenium, rhodium or iridium and at least one bidentate enantiopure ligand. At present, mainly bidentate phosphanyl substituted ligands are in use. Since for asymmetric hydrogenation catalysts the number of applicable metals is rather limited further catalyst design focuses primarily on the development of novel ligands and on the improvement of reaction conditions. Unfortunately, most enantioselective catalysts are highly substrate dependent and therefore can only be applied in a limited number of transformations. One way to circumvent this problem is to develop not only single ligands and catalysts but a great number of structurally closely related ligand ensembles, the so called ligand families. In this context, the development of novel ligand families for hydrogenation and transfer hydrogenation catalysts is proposed. All these ligands will be based on a ferrocene backbone to which an oxazoline unit as well as an phosphino-alkyl or alike unit is attached. To reach this goal, several sequential development steps will be required: (i) the development of highly modular synthesis protocols that allow the preparation of a variety of structurally related ligands via one single synthesis route; (ii) the preparation of coordination complexes to be used in asymmetrically catalysed reactions; (iii) an extensive and efficient screening of ligands and complexes in catalytic reactions; and (iv) a critical evaluation of results in order to find potential applications. The catalyst screening procedure will mainly focus on ruthenium based hydrogenations of ketones and iridium catalysed hydrogenations of imines. Especially for the latter transformation, the reduction of imines to commercially important enantiopure amines efficient catalysts with a broader range of applicability are needed.

For the production of bioactive compounds such as drugs, fragrances, herbicides or pesticides more and more selective and environmentally benign synthesis methods are required. Since many of these derivatives can exist in two mirror image like forms which usually show different biological activity highly selective synthesis methods are an absolute necessity. Homogeneous asymmetric catalysis constitutes one very powerful methodology for the synthesis of such so called enantiopure derivatives. Besides enzymes, transition metal complexes have been used most successfully as asymmetric catalysts. For large scale industrial reactions especially asymmetric hydrogenations are of prime interest since in these reactions cheap hydrogen gas is used as the reagent and almost no reaction waste is formed. In most cases, hydrogenation catalysts are coordination compounds of either ruthenium, rhodium or iridium and at least one bidentate enantiopure ligand. At present, mainly bidentate phosphanyl substituted ligands are in use. Since for asymmetric hydrogenation catalysts the number of applicable metals is rather limited further catalyst design focuses primarily on the development of novel ligands and on the improvement of reaction conditions. Unfortunately, most enantioselective catalysts are highly substrate dependent and therefore can only be applied in a limited number of transformations. One way to circumvent this problem is to develop not only single ligands and catalysts but a great number of structurally closely related ligand ensembles, the so called ligand families. Within this project two novel ligand families have been developed which performed excellent in the rhodium- or ruthenium-catalyzed asymmetric hydrogenation of alkenes and ketones. Structurally, one ligand family is based on a ferrocenyl-oxazoline backbone while the second group of ligands is based on a biferrocene unit. Best results were achieved in the asymmetric hydrogenation of ketones and of 2-alkylcinnamic acids.