C–F Bond Cleavage Enabled Redox-Neutral [4+1] Annulation via C–H Bond Activation

Abstract

Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported. The 2-fold C-F bond cleavage not only enables the generation of desired product under an overall oxidant-free condition but also results in a net migration of carbon-carbon triple bond. In addition, the present reaction protocol exhibits a tolerance of a wide spectrum of functional groups due to the mild reaction conditions employed.

Catalytic Asymmetric Synthesis of Isoindolinones

“…In 2017, the Cp*Rh III ‐catalyzed C−H activation reaction provided an excellent strategy to afford alkynyl isoindolinones . Inspired by this report, such chiral products were prepared by Wang's group by a chiral Cp X Rh III ‐catalyzed C−H activation approach from N ‐methoxy benzamides 120 and α,α‐difluoromethylene alkynes 121 in 2018 .…”

“…In 2017, the Cp*Rh III -catalyzed CÀHa ctivation reaction provided an excellent strategy to afford alkynyl isoindolinones. [54] Inspired by this report, such chiral products were prepared by Wang's group by ac hiral Cp X Rh III -catalyzed CÀHa ctivation approach from N-methoxy benzamides 120 and a,a-difluoromethylene alkynes 121 in 2018. [55] Remarkably,t he alkynyli soindolinones 128 were generated in up to 86 %y ield with 99.6 % ee in MeOH, whereas the Z-fluoroalkenyl products 129 were afforded in up to 93 %y ield with 86 % ee in iPrCN (Scheme 33).…”

Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

“…Rh III -catalyzed CÀHf luoroallenylation using gem-difluoroalkynes (Scheme 21) [50] as well as C À Hfluorovinylation using 1,1-difluoro-1-alkenes (not shown). [51] Thegroup of Wang and Li achieved the selective synthesis of six-and five-membered lactams using 2,2-difluorovinyl tosylates catalyzed by asingle Rh III species [52] and aR h III /Ag I catalyst, respectively (Scheme 22).…”

Reaching Green: Heterocycle Synthesis by Transition Metal‐Catalyzed C−H Functionalization in Sustainable Medium

“…Recently,a[4+ +1] annulation of N-methoxy amides 4 with a,a-difluoromethylenea lkyne 34 in the presence of Rh catalyst was reported by Feng and co-workers to synthesize isoindolinones 35 containing an alkyne group (Scheme 13). [41] The reaction proceeds through amide-directedC ÀHm etalation D1 followed by alkyne insertion D2 and b-F elimination to give allene intermediate D3,w hich furtheru ndergoes amino-rhodation to give D4.I nt he end, the second b-F elimination of D4 leads to the desired product 35 and regenerates the catalyst. The merits of the reactiona re dual C-F cleavage, redox-neutral, and introducing synthetically useful alkyne in isoindolinones using sustainable reactionm edium.…”