Development of a Catalytic Enantioselective Method for the Construction of All-Carbon Quaternary Stereocenters: The Asymmetric Palladium-Catalyzed Conjugate Addition of Alkyl-, Vinyl-, and Alkynylboron Nucleophiles to alpha, beta-Unsaturated Electrophiles

• Applicant: Dr. Denis Kröger
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318856427

The enantioselective construction of all-carbon quaternary stereocenters (carbon atoms to which four distinct carbon substituents are attached) is of significant interest for various fields of research. Due to its three-dimensionality, the underexplored chemical space is increased substantially. Associated therewith, new opportunities will be offered, which are not available in the case of broadly used achiral flat molecules. In spite of that, only a few of the drugs with the highest turnover have all-carbon quaternary stereocenters. None of these stereocenters have been constructed by chemical synthesis. In all cases, those structures are derived from natural products. Based on this situation, two main insights can be gained. On the one hand, the potential of such chiral molecules is largely underexplored, and on the other hand, there is a lack of broadly applicable synthetic strategies for its build-up. Thus, the objective of the research project is to develop and to establish a universal method for the construction of these kinds of stereocenters under easily practicable synthetic conditions and in an atom-economical manner. Inspired by a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to beta-substituted cyclic enones, which is limited to arylboron nucleophiles, the research project will be taken up. This new method aims to overcome the limitations so far and will allow the implementation of numerous substituents. The project shall be realized by the use of new palladium based catalysts containing bi- or tridentate N-heterocyclic carbene (NHC) ligands together with stable alkyl, vinyl and alkynylboron nucleophiles with functionalized sidechains. Particularly due to the opportunity of using boron nucleophiles with functionalized sidechains (e.g. amino acids or heteroaromatic compounds), the proposed method will strongly contrast to former methods and will additionally provide the possibility for further multi-faceted reactions.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Brian M. Stoltz, Ph.D.