Cp*Rh(III)-Catalyzed C–H Bond Difluorovinylation of Indoles with α,α-Difluorovinyl Tosylate

Abstract

Unprecedented Rh­(III)-catalyzed C–H bond difluorovinylation of indoles has been successfully developed, and this method provided an example of direct difluorovinylation reaction through C–H bond activation which was rarely reported. In this context, N-ethoxycarbamoyl served as the directing group and 2,2-difluorovinyl tosylates were used for the construction of difluorovinyl-substituted indoles. This method provided a practical strategy for difluorovinylation of indoles with moderate to good yields and is characterized by the broad synthetic utility, mild conditions, and high efficiency.

Stereoselective β–F Elimination Enabled Redox-Neutral [4 + 1] Annulation via Rh(III)-Catalyzed C–H Activation: Access to Z-Monofluoroalkenyl Dihydrobenzo[d]isoxazole Framework

“…On the contrary, more recently fluorinated reagents , have been widely used as innovative and powerful cross-coupling partners for the design and development of new TM-catalyzed direct C–H functionalization reactions because they could display a reactivity and reaction mode distinct from that of the nonfluorinated analogues, mainly due to the unique electronic and steric characteristics of the fluorine atom. , Among these developed fluorinated partners, α , α -difluoromethylene alkynes have occupied a prevalent position . For example, inspired by the pioneering work of Loh and Feng (Scheme a), , the groups of Wang and Rovis have independently displayed the successful exploration of α,α-difluoromethylene alkynes as the cross-coupling partners in TM-catalyzed C–H functionalization (Scheme b,c).…”

Indole‐N‐Carboxylic Acids and Indole‐N‐Carboxamides in Organic Synthesis

“…In 2019, the Liu group reported a Rh-catalyzed CÀ H Bond difluorovinylation of Indoles between indole-N-carboxamides 56 and α,α-difluorovinyl tosylate 57 (Scheme 15). [23] By using 5 mol % [Cp*RhCl 2 ] 2 and 2 equivalents of NaOAc at ambient temperature, toluene as solvent, difluorovinyl indoles 58 could be formed smoothly under the directing effect of N-ethoxycarbamoyl. To the best of our knowledge, this reaction is the exclusive example for the synthesis of biological useful indole derived difluoroalkenes by CÀ H activation process.…”

“…In 2019, the Liu group reported a Rh‐catalyzed C−H Bond difluorovinylation of Indoles between indole‐ N ‐carboxamides 56 and α,α‐difluorovinyl tosylate 57 (Scheme ) . By using 5 mol % [Cp*RhCl 2 ] 2 and 2 equivalents of NaOAc at ambient temperature, toluene as solvent, difluorovinyl indoles 58 could be formed smoothly under the directing effect of N ‐ethoxycarbamoyl.…”

Rh(III)-Catalyzed C–H Bond Activation for the Construction of Heterocycles with sp3-Carbon Centers

“…In recent years, our group has been devoted to developing some highly efficient synthetic strategies to extend our heterocyclic compounds library for the screening of biologically active lead compounds [75−85]. In 2017, we built a novel isoindolone scaffold bearing a quaternary carbon via Rh(III)-catalyzed C−H bond cleavage and subsequent [4 + 1] cyclization tandem reactions between In recent years, our group has been devoted to developing some highly efficient synthetic strategies to extend our heterocyclic compounds library for the screening of biologically active lead compounds [75][76][77][78][79][80][81][82][83][84][85]. In 2017, we built a novel isoindolone scaffold bearing a quaternary carbon via Rh(III)-catalyzed C−H bond cleavage and subsequent [4 + 1] cyclization tandem reactions between benzamides and propargyl alcohols (Scheme 13) [76].…”