Ruthenium(II)-Catalyzed α-Fluoroalkenylation of Oxime Ethers with gem-Difluorostyrenes via C–H Activation and C–F Cleavage

Abstract

A novel route for ruthenium(II)-catalyzed αfluoroalkenylation of oxime ethers with gem-difluorostyrenes via C−H activation and C−F cleavage has been developed for the first time. Notably, the alkenyl units of products exhibit exclusive Zconfiguration. This reaction features a broad substrate scope and good functional group tolerance. A plausible reaction mechanism is confirmed by an available cycloruthenated intermediate. Besides, the O-methyl oximyl-directing group can be readily removed to access the α-fluoroalkenylated acetophenones.

HFIP in Organic Synthesis

“…Later, a Rh­(III)-catalyzed monofluoroalkenylation of quinazolinones with 2,2-difluorovinyl tosylate in HFIP afforded functionalized 2-arylquinazolinones in up to 92% yield . Likewise, a Ru­(II)-catalyzed fluoroalkenylation of oxime ethers was described utilizing gem -difluorostyrenes in HFIP . High ( Z )-selectivity was observed using this method; MeOH, TFE, and EtOH resulted in either no reaction or significantly diminished yield.…”

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…Ji's group illustrated a general and efficient example of αfluoroalkenylation of oxime ethers with various gem-difluorostyrenes through a Ru(II)-catalyzed C−H/C−F bond cleavage strategy (Scheme 465). 749 Remarkably, the alkenyl moiety in the resulting products existed exclusively in the Zconfiguration. This method worked with a variety of substrates along with good tolerance of functional groups.…”

Recent advances in transition-metal catalyzed directed C–H functionalization with fluorinated building blocks

“…Recently, the use of oxime ethers 41 as directing groups for site-selective α-fluoroalkenylation with gem -difluorostyrenes 36 under a Ru catalyst was demonstrated by Fu et al (Scheme 11a). 101 The conditions were mild; however, a high loading of Ru catalyst (15 mol%) was required for a greater yield with high Z -selectivity. They carried out the reactions with various substrates, furnishing good to high yields.…”