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

Cheng Xu; Guodong Yin; Feng-Cheng Jia; Yan-Dong Wu; An-Xin Wu

doi:10.1021/acs.orglett.1c00486

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

Org Lett. 2021 Apr 2;23(7):2559-2564. doi: 10.1021/acs.orglett.1c00486. Epub 2021 Mar 19.

Authors

Cheng Xu^{1

2}, Guodong Yin¹, Feng-Cheng Jia², Yan-Dong Wu², An-Xin Wu²

Affiliations

¹ College of Chemistry and Chemical Engineering, Hubei Key Laboratory of Pollutant Analysis and Reuse Technology, Hubei Normal University, Huangshi 435002, P. R. China.
² Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.

PMID: 33739840
DOI: 10.1021/acs.orglett.1c00486

Abstract

An unprecedented I₂/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(sp³)-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.