State of the art
- Photoredox approaches requires the use of rare and precious metals that limits the applicability and scalability of the approach.
- Flow chemistry has shown the benefit to find new avenues in photochemistry, for instance the discovery of light induced cross couplings.
- These approaches require the use of non-precious and abundant metals, such as zinc, magnesium, iron and nickel, to performed reactions that are not suitable in the absence of light. However, more research should be devoted to this new chemistry approach to find new reactions that will help the access to new chemical space for Drug Discovery and Development.
Scheme 15. Examples of light induced cross-coupling reactions.
Progress beyond the state of the art
- Three light induced cross-couplings have been recently reported by our group in collaboration with different universities, incl. current partners UvA and USTAN.
- These new methodologies have been already applied to internal medicinal chemistry programs, demonstrating their value to access chemical space that was not suitable by other approaches.
- Scalability of these new cross-couplings was demonstrated using a Corning photoreactor. This will allow to prepare bioactive molecules up to kilogram scale.
- Find new cross-coupling reactions using this approach. At least 3 new reactions, such as light-enhanced Negishi, Kumada-Corriu and Suzuki- Miyaura couplings Csp2-Csp3 couplings or the coupling of heterocycles (Scheme 15).
- Use UV-Vis, IR NMR and other tools to determine the mechanism of the reactions and scope for other applications according to the findings.
- Other photocatalytic transformations developed by the partners will be explored on site with available drug-like scaffolds.