Rhodium‐Catalyzed Defluorinative Vinylation of gem‐Difluoroalkenes for the Synthesis of 2‐Fluoro‐1,3‐dienes

Abstract

of main observation and conclusion Herein, we present a strategy for the formation of 2-fluoro-1,3-diene derivatives via rhodium-catalyzed direct C(sp 2 )-C(sp 2 ) cross-coupling of gem-difluoroalkenes and acrylamides. By merging Rh(III)-catalyzed C(sp 2 )-H bond activation and nucleophilic addition/F-elimination of gem-difluoroalkene, an efficient defluorinative vinylation reaction is uncovered, which leads to the generation of 2-fluoro-1,3-dienes in moderate to good yields with excellent stereoselectivity under mild conditions. Preliminary mechanistic study suggests unique effects of fluorine substituents which allow the reactivity profile not observed with the congeners bearing heavier halides.

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

“…Moreover, Loh and co-workers investigated the Cp*Rh(III)catalyzed defluorinative C−H vinylation of acrylamides with gem-difluoroolefins in order to construct of a variety of 2fluoro-1,3-dienes (Scheme 459). 743 An initial alkenyl C(sp 2 )− H bond activation, accompanied by nucleophilic addition and β-fluoride elimination, gave the coupling products in decent yields with exceptional stereocontrol. Mechanistic studies illustrated that due to the peculiar effects of the fluorine substituent, the reactivity of this transformation was not observed for analogues containing heavier halide atoms.…”

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

“…In 2019, Loh et al reported a strategy for the preparation of 2-fluoro-1,3-diene derivatives 81a–81d under Rh catalysis by direct cross-coupling of gem -difluorovinyl tosylate 45 and acrylamides 80 (Scheme 19a). 115 Also, they demonstrated the further derivatization of these synthesized fluorinated diene scaffolds to thioethers 82 (Scheme 19b). Furthermore, the plausible mechanism involves the rhodacycle intermediate 83 , which coordinates with gem -difluoroalkene followed by migratory insertion to give intermediate 85 .…”

Cross-Coupling Reactions of Double or Triple Electrophilic Templates for Alkene Synthesis

“…23 In 2019, Feng et al demonstrated that fluoroalkenylation could be performed without the addition of a silver(I) additive. 24 Scheme S9 Unusual reactivity of difluorovinyl tosylates en route to the synthesis of trisubstituted alkenes and heterocyclic compounds…”