Molecular Complexity via Enantioselective Palladium Catalysed C-N Bond Formations

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

The project concerns the development of new aza-Heck cyclizations and cascades based upon methodology recently developed at Bristol. The project is split into three parts:

1. The synthesis of pyrrolidines and piperidines via enantioselective Pd-catalysed aza-Heck cyclizations
2. Enantioselective Pd-catalysed aza-Heck cascades.
3. New cascade C-N bond forming processes enabled by N-O oxidative addition:

The programme concentrates on the development of novel asymmetric C-N bond forming processes that are of potentially widespread utility to medicinal chemistry. The provision of a general enantioselective aza-Heck protocol will address an unmet challenge in organic synthesis, and will have high impact. The programme is underpinned by important preliminary results; as such, significant progress can be achieved in the PhD project. The programme will train the student in the areas of asymmetric organometallic catalysis, N heterocyclic chemistry and organometallic reaction mechanism.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509619/1 01/10/2016 30/09/2021
1941711 Studentship EP/N509619/1 02/10/2017 30/09/2021 Benjamin Jones
 
Description The work funded through this award is focused on the development of aza-Heck reactions for the synthesis of nitrogen-containing heterocycles. Nitrogen-containing heterocycles are particularly prevalent in drug compounds, and therefore new methods of synthesis are of significant interest to the field of medicinal chemistry. Cascade aza-Heck reactions provide nitrogen heterocycles containing various degrees of functionality, meaning they can produce more complex structures in a single step. As a result of this research, three novel classes of cascade reaction have been discovered and developed to a useful synthetic standard. One of these reactions is currently being utilised towards the synthesis of a complex natural product molecule. However, efforts to carry out these transformations enantioselectively are ongoing.
Exploitation Route Multiple promising aza-Heck cascade reactions have been developed as a result of this funding. Currently the work is yet to be published, however, it has the potential for application in the chemical industry for the synthesis of substituted nitrogen heterocycles as drug candidates for example. The impact of this research will be significantly increased if it can be carried out asymmetrically, this is a current area of focus and could be continued by other researchers within the group.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology