Rhodium-catalysed C(sp2)–C(sp2) bond formation via C–H/C–F activation

Abstract

Fluoroalkenes represent a class of privileged structural motifs, which found widespread use in medicinal chemistry. However, the synthetic access to fluoroalkenes was much underdeveloped with previous reported methods suffering from either low step economy or harsh reaction conditions. Here we present a RhIII-catalysed tandem C–H/C–F activation for the synthesis of (hetero)arylated monofluoroalkenes. The use of readily available gem-difluoroalkenes as electrophiles provides a highly efficient and operationally simple method for the introduction of α-fluoroalkenyl motifs onto (hetero)arenes under oxidant-free conditions. Furthermore, the employment of alcoholic solvent and the in-situ generated hydrogen fluoride are found to be beneficial in this transformation, indicating the possibility of the involvement of hydrogen bond activation mode with regards to the C–F bond cleavage step.

Rhodium‐Catalyzed C(sp2)‐ or C(sp3)−H Bond Functionalization Assisted by Removable Directing Groups

“…[135] Thea ctivation of the C À Fb ond through formation of ahydrogen bond in apolar protic solvent or by in situ generated hydrogen fluoride was found to be crucial for the success of the reaction. [135] Thea ctivation of the C À Fb ond through formation of ahydrogen bond in apolar protic solvent or by in situ generated hydrogen fluoride was found to be crucial for the success of the reaction.…”

Synthesis of Fluorine-Containing 6-Arylpurine Derivatives <i>via</i> Cp*Co(III)-Catalyzed C–H Bond Activation

“…[4][5][6][7][8][9] More recently, C-H functionalization reactions accompanied by selective C-F bond cleavage of multi-fluorinated coupling partners were explored. Loh and colleagues reported monofluoroalkene synthesis using gem-difluoroalkenes via aromatic C-H activation under Cp*Rh(III) (Cp*=pentamethylcyclopen-tadienyl) catalysis to afford monofluoroalkenes, 18) which can serve as peptide mimics 19,20) (Chart 1a). They proposed that β-F elimination after C-H bond cleavage and the insertion of C-C double bonds furnishes the product.…”

Visible light photocatalytic decarboxylative monofluoroalkenylation of α-amino acids with gem-difluoroalkenes

“…As a typical representative of fluorinated compounds, monofluoroalkenes are regarded as nonhydrolyzable amide bioisosteres 5 and their lipophilic properties prompt chemists to develop synthetic approaches to monofluoroalkenes. Among the starting materials for the synthesis of monofluoroalkenes, gem-25 difluoroalkenes are readily available and versatile substrates, 6 and their C-F bond functionalization with boronic acids, 7 heteroarenes, 8 Very recently, Hashmi and co-workers described a visible light photoredox C(sp 3 )-H monofluoroalkenylation of dimethylanilines and trialkyl amines via an oxidation/deprotonation sequence. 40 We realized that fluorinated molecules containing amino acid fragments would be of great interest for further derivatization to diverse compounds, so we here report our work toward visible light photoredox decarboxylative monofluoroalkenylation of Nprotected α-amino acids with gem-difluoroalkenes.…”