A Scalable High-Yielding and Selective Oxidative Heck Cross-Coupling – A Key Step for the Synthesis of trans- Stilbenes
Journal article, Peer reviewed
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https://hdl.handle.net/11250/2989838Utgivelsesdato
2021Metadata
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- Department of Chemistry [442]
- Registrations from Cristin [10237]
Originalversjon
European Journal of Organic Chemistry. 2021, 2021 (40), 5519-5529. 10.1002/ejoc.202100493Sammendrag
A selective oxidative Heck cross-coupling method was developed and optimized as a pivotal step for a synthetic route leading to the trans-stilbene framework. The developed method and synthesis were needed in a SAR study in progress that concerned design and development of an inhibitor for the human cell xCT antiporter system. The developed oxidative Heck cross-coupling method was examined with a variety of substrates and reagents to produce a library of different substituted trans-stilbenes, which revealed the method to hold a very good tolerance for an assortment of functional groups. The final synthetic route was successfully scaled-up (from mg scale) and performed in a 150 g (>1000×up-scaled) batch run to obtain an overall yield of 73 % (over three steps), which corresponds to a mean step yield of 90 %. The inhibitor candidate DC10 [(E)-5-(2-([1,1′-biphenyl]-4-yl)vinyl)-2-hydroxy-benzoic acid] was produced in multi-gram quantities (≈33 g) that subsequently was forwarded for animal efficacy and toxicology studies. The scaled-up process constitutes the first example of an oxidative Heck cross-coupling on >100-gram scale.