Background and aims
Fluorine-containing organic compounds are highly valued for their ability to improve stability, lipophilicity, and biological activity. Monofluoroalkenes, in particular, act as metabolically stable amide bioisosteres and are widely used as intermediates in pharmaceuticals, agrochemicals, and materials science. Despite their utility, efficient and general methods to access monofluoroalkenes with high stereochemical control remain limited. ¹ This study aimed to develop a modular and practical catalytic strategy to address this limitation.
Methods
We designed a dual copper/palladium catalytic system that integrates alkyne borylcupration with palladium-catalyzed C–C bond activation and selective C–F bond cleavage of gem-difluorocyclopropanes. ²
Results
The dual catalytic system delivered boryl-substituted monofluoroalkenes in good to high yields with excellent regio- and stereoselectivity. It showed broad substrate scope, functional group tolerance, and enabled late-stage modification of complex molecules.
Conclusion
This copper-palladium strategy offers an efficient and versatile route to monofluoroalkenes, thereby expanding synthetic options for fluorine chemistry and its applications in drug discovery.
References