Towards Transition Metal Catalyzed Asymmetric C-H Activation

01.02.2009 - 01.02.2012
Forschungsförderungsprojekt
The present proposal is aiming at the development of asymmetric C-H activation reactions by means of transition metal catalysis. In this context, C-H activation reactions represent a methodology with great potential in synthesis since, if applicable, synthetic sequences can be shortened considerably. This was already demonstrated in innovative examples in the literature however, mainly in an asymmetric fashion. Most examples were reported for sp2 C-H activation since the sp2 C-H bond proved to be easier to activate and fewer side reactions are observed. In recent years also sp3 C-H activation made considerable progress and also the first asymmetric versions were reported however, all of them had there own limitations. Therefore, further research in this area is needed and has the potential to improve on the efficiency of chemical synthesis. The current proposal tackles the problem of asymmetric C-H activation via two different approaches. The first one takes advantage of a directing group which shall be installed in the starting material with defined stereochemistry. This directing group shall then direct the transition metal catalyst to only one specific C-H bond of a CH2 group leading finally to a diastereomerically-enriched or ideally diastereomerically-pure product. As starting materials compounds from the available chiral pool are envisioned such as carboxylic acids of pyrrolidine, piperidine, THF, THP, and others. Carboxylic acids were chosen as starting materials since they can be easily converted into a number of potential directing groups (esters, amides, oxazolines, etc.). Since the stereoinformation is already present in the substrates, achiral catalysts can be used even though chiral catalysts may lead to improved results (match – mismatch). The nature of the catalyst will be a main topic of investigation. As starting point for this research Pd, Rh, and Ru catalysts will be investigated since such systems were frequently used in the context of C-H activation chemistry. The second approach starts from achiral starting materials and it is aimed to introduce chirality into the products via the use of chiral catalysts. Ideally, the catalytic system will be formed in situ by the use of catalyst precursors and addition of chiral ligands. However, also pre-synthesized chiral catalysts will be tested in this transformation. Initially, the same transition metals as in the first approach will also be tested here. In this case, substrates carrying benzylic CH2 groups are the first target systems since those CH2 groups are believed to be quite reactive towards transition metal catalyzed C-H activation. Generally, no directing groups in the classical sense will be present in the starting materials. However, it is envisioned in one substrate class to have heteroatoms adjacent to the CH2 group to be activated. Additionally, heterocycles such as pyridine can have a directing effect when located in a favorable distance to the CH2 group in question and such compounds will be another class of substrates interesting for this project. Initially, arylation reactions will be investigated in both project parts. Therefore, suitable aryl donors have to be found. In later stages also alkylations, alkenylations, and carbonylations will be tested.

Personen

Projektleiter_in

Projektmitarbeiter_innen

Institut

Grant funds

  • FWF - Österr. Wissenschaftsfonds (National) Austrian Science Fund (FWF)

Forschungsschwerpunkte

  • Biological and Bioactive Materials: 70%
  • Materials Characterization: 30%

Schlagwörter

DeutschEnglisch
asymmetrische Syntheseasymmetric synthesis
C-H AktivierungC-H activation
Metallkatalysemetal catalysis

Publikationen