Palladium‐Catalyzed Fluoroarylation of gem‐Difluoroalkenes

Abstract

A Pd-catalyzed fluoroarylation of gem-difluoroalkenes with aryl halides is reported. By taking advantage of the in situ generated α-CF -benzylsilver intermediates derived from the nucleophilic addition of silver fluoride to gem-difluoroalkenes, this strategy bypasses the use of a strong base, thus enabling a mild and general synthetic method for ready access to non-symmetric α,α-disubstituted trifluoroethane derivatives.

Palladium‐Catalyzed Direct Approach to α‐Trifluoromethyl Alcohols by Selective Hydroxylfluorination of gem‐Difluoroalkenes

“…By screening the ligands, such as L2, L3 and L4, L1 was revealed to be the optimal ligand (entries 9-11). Although we obtained desired compound with a yield of 32 % in NMP, the subsequent solvent screening indicated that this reaction did not work in other solvents such as CH 3 CN, DMF and THF (en-tries [12][13][14][15]. Furthermore, when the reaction mixture was warmed to 40°C, the desired product 2a was obtained in the same yield (entry 16 vs. entry 8).…”

“…In addition, Loh and co‐workers presented a different and novel strategy based on palladium‐catalyzed allylic alkylation by caesium fluoride nucleophilic addition of gem ‐difluoroalkenes in 2016 (Figure c ) . Furthermore, in 2017 Loh and co‐workers described the palladium‐catalyzed fluoroarylation of gem ‐difluoroalkenes and arylation with aryl halides (Figure d ) . It is worthy to note that the in situ generated α‐CF 3 ‐benzylsilver, the key intermediate, derived from the nucleophilic addition of silver fluoride onto gem ‐difluoroalkenes.…”

“…[11] Furthermore, in 2017 Loh and co-workers described the palladiumcatalyzed fluoroarylation of gem-difluoroalkenes and arylation with aryl halides (Figure 1d). [12] It is worthy to note that the in situ generated α-CF 3 -benzylsilver, the key intermediate, derived from the nucleophilic addition of silver fluoride onto gem-difluoroalkenes. However, researches are still confronted with many potential challenges, such as the low stability of intermediates and their notorious reluctance to participate in the transmetalation.…”

Visible‐Light‐Assisted Gold‐Catalyzed Fluoroarylation of Allenoates

“…Shortly afterwards, an inspiring chelation‐assisted palladium‐catalyzed fluoroarylation of styrene derivatives was reported by Toste and co‐workers, albeit using expensive Selectfluor as the fluorination reagent (Scheme a) . Recently, our group achieved a straightforward construction of 1,1,1‐trifluoro‐2‐arylalkane derivatives by applying palladium‐catalyzed cross‐coupling of aryl iodides with in situ generated organosilver intermediate (Scheme b) . Notwithstanding the notable advancements achieved in this area, the reported reactions still suffer from limitations such as restricted reaction generality, the employment of expensive fluorination reagents, and the unavoidable formation of accompanying regioisomers in some cases.…”

Transition‐Metal‐Catalyzed Three‐Component Difunctionalizations of Alkenes

“…Very recently, Loh et al. reported a novel palladium‐catalyzed fluoroarylation of gem ‐difluorostyrenes with aryl halides by using AgF as a fluorinating reagent (Scheme ) . In contrast with the previous 1,2‐arylfluorination reported by Toste et al., this reaction produced a 2,1‐arylfluorinated product instead, which provides an efficient method to access asymmetric α,α‐diarylsubstituted trifluoroethane derivatives.…”