Khumsubdee, Sakunchai (2013-12). Synthesis and Application of New Ligands Derived from N-Heterocyclic Carbenes, Phosphines and Phosphites for Asymmetric Hydrogenations. Doctoral Dissertation. Thesis uri icon

abstract

  • N-Heterocyclic carbene and phosphorus ligands have been synthesized and used for many catalytic reactions including chiral analogs of Crabtree's catalyst for asymmetric hydrogenation. These catalysts have been studied extensively, especially on hydrogenation of "largely unfunctionalized" alkenes, for more than a decade. These substrates, however, could not be easily modified leading to limited applications for organic synthesis. As a result, asymmetric hydrogenations of substrates that have non- coordinating functional groups have gained more attention because the products are chirons that could be used to synthesize many natural products. Even though many chiral analogs of Crabtree's catalysts have been studied, none of these catalysts is perfect. Different catalysts could be suitable for different substrates. This point motivated us to investigate asymmetric hydrogenation of different substrates using our N,carbene Crabtree's catalyst analog; for example, ?-methyl-?-alkyl-?-amino acid derivatives can be obtained with high stereoselectivities. Moreover, the same point also inspired us to synthesize the new N-heterocyclic carbene ligands to compare the effect on different catalysts that have related structure. Design new ligands to obtain effective catalysts, however, needs high experience and it is possible time consuming with unpredictable outcomes. Using the screening method with mono-chelating phosphorus ligands synthesized from cheap and easily obtained starting materials might be possible solution. However, we cannot rule out the possibility that bi-chelating ligand of the related structure might give better selectivities. Cross metathesis is an easy method that can link two parts together to convert mono- chelating ligand to bi-chelating one. Using metathesis combined with catalysis "metacatalysis" is one method to compare catalytic activity of mono- and bi-dentate ligands. However, the result indicated that most this method was suitable in some cases but not all.
  • N-Heterocyclic carbene and phosphorus ligands have been synthesized and used for many catalytic reactions including chiral analogs of Crabtree's catalyst for asymmetric hydrogenation. These catalysts have been studied extensively, especially on hydrogenation of "largely unfunctionalized" alkenes, for more than a decade. These substrates, however, could not be easily modified leading to limited applications for organic synthesis. As a result, asymmetric hydrogenations of substrates that have non- coordinating functional groups have gained more attention because the products are chirons that could be used to synthesize many natural products.

    Even though many chiral analogs of Crabtree's catalysts have been studied, none of these catalysts is perfect. Different catalysts could be suitable for different substrates. This point motivated us to investigate asymmetric hydrogenation of different substrates using our N,carbene Crabtree's catalyst analog; for example, ?-methyl-?-alkyl-?-amino acid derivatives can be obtained with high stereoselectivities. Moreover, the same point also inspired us to synthesize the new N-heterocyclic carbene ligands to compare the effect on different catalysts that have related structure.

    Design new ligands to obtain effective catalysts, however, needs high experience and it is possible time consuming with unpredictable outcomes. Using the screening method with mono-chelating phosphorus ligands synthesized from cheap and easily obtained starting materials might be possible solution. However, we cannot rule out the possibility that bi-chelating ligand of the related structure might give better selectivities. Cross metathesis is an easy method that can link two parts together to convert mono- chelating ligand to bi-chelating one. Using metathesis combined with catalysis "metacatalysis" is one method to compare catalytic activity of mono- and bi-dentate ligands. However, the result indicated that most this method was suitable in some cases but not all.

publication date

  • December 2013