State of the art
- Alkenes and vinyl nucleophiles and electrophiles are valuable precursors for stereospecific cross-coupling.
- Routes to Z-isomers remain challenging due to the contra-thermodynamic or thermo-neutral nature of these processes that restrict the range of chemical space available for drug discovery.
- Correlating triplet sensitizer with substrates of interest requires clarification and scale up of the transformations remains an important consideration.
Scheme 10. Generic alkene isomerisation.
Progress beyond the state of the art
- We have generalised a conceptual platform for the contra-thermodynamic and thermo-neutral isomerisation of activated alkenes based on selective energy transfer catalysis (Scheme 10).
- Allylic strain is a key determinant in achieving high levels of Z-selectivity.
- Extension to bis-vinyl nucleophiles has been validated and its synthetic utility validated in the stereocontrolled synthesis of triarylethylenes. These
motifs are found in numerous drug molecules such as Tamoxifen.
- The starting materials can be easily prepared through existing
technologies, but routes to the Z-isomers are conspicuously absent.
- Following successful development of photocatalysts, batch and flow conditions will be devised in cooperation with the other partners.
- Photocatalyst platforms devised by other partners will be examined in at least two energy transfer reactions.