Merging Annulation with Ring Deconstruction: Synthesis of (E)-3-(2-Acyl-1H-benzo[d]imidazol-4-yl)acrylaldehyde Derivatives via I2/FeCl3-Promoted Dual C(sp3)-H Amination/C-N Bond Cleavage

An unprecedented I-2/FeCl3-promoted cascade reaction of aryl methyl ketones with 8-aminoquinolines for the convenient synthesis of (E)-3-(2-acyl-1H-benzo[d]imidazol-4-yl)acrylaldehydes was developed by merging annulation with ring deconstruction. This novel strategy unlocked the new reactivity of 8-aminoquinolines and provided an attractive platform for the ring opening of unactivated N-heteroaromatic compounds. Preliminary mechanistic investigation suggested that dual C(sp(3))-H amination/C-N bond cleavage were key reaction steps. Furthermore, late-stage modification of the obtained products successfully delivered pyrazole and isoxazole derivatives, increasing the practicability and application potential of this methodology in organic synthesis.

Automated summary

A novel I-2/FeCl3-promoted cascade reaction was developed for the convenient synthesis of (E)-3-(2-acyl-1H-benzo[d]imidazol-4-yl)acrylaldehydes by merging annulation with ring deconstruction, unlocking the new reactivity of 8-aminoquinolines and providing a platform for the ring opening of unactivated N-heteroaromatic compounds. Preliminary mechanistic investigation suggested that dual C(sp(3))-H amination/C-N bond cleavage were key reaction steps, and late-stage modification successfully delivered pyrazole and isoxazole derivatives, increasing the practicability and application potential of this methodology in organic synthesis.