Copper-Catalyzed Fluoroalkylphosphorothiolation of Alkynes for the Synthesis of (E)-β-Fluoroalkyl Vinyl Phosphorothioates

Abstract

A convenient copper-catalyzed three-component radical-based fluoroalkylphosphorothiolation of terminal alkynes with ( i PrO)2P­(O)­SH and fluoroalkylation reagent for the synthesis of a variety of (E)-β-fluoroalkyl vinyl phosphorothioates with excellent regioselectivity and stereoselectivity has been developed. All the starting materials used in this reaction are highly stable and readily available. Thus, this process features with mild reaction conditions, simple operation and good functional group tolerance (>40 examples). Furthermore, this modular reaction system allows the late-stage functionalization of bioactive molecules.

Visible Light-Induced Copper-Catalyzed Regio- and Stereoselective Difluoroalkylthiocyanation of Alkynes

“…Later, the perfluoroalkylcyanation of arylacetylenes with R f I and TMSCN was reported by Bao in the presence of a copper catalyst and stoichiometric peroxide (Scheme b, ii) . Very recently, Li successfully introduced a CF 3 group and a coordinating group-tethered amide moiety into alkynes through a copper-catalyzed oxidant-promoted procedure (Scheme b, iii), and the group of Shi and Gao achieved fluoroalkylphosphorothiolation of terminal alkynes under cooper catalysis or iridium-photoredox/copper dual catalysis (Scheme b, iv) . In addition, the Reiser group demonstrated the effectiveness of copper-phenanthroline complexes as photoredox catalysts and made great contributions in the transformation of C–C multiple bonds .…”

“…Various CF 2 -alkyl radical precursors could be utilized to provide diverse β-fluoroalkyl vinyl thiocyanates with specific regio- and stereochemistry. Remarkably, the internal alkynes, previously challenging under copper/photoredox dual catalysis, , are successfully accommodated, offering a versatile and efficient synthetic route to fully substituted olefins containing CF 2 moieties.…”