Monodentate Transient Directing Group Assisted Ruthenium(II)-Catalyzed Direct ortho-C-H Imidation of Benzaldehydes for Diverse Synthesis of Quinazoline and Fused Isoindolinone

2-Fluoro-5-(trifluoromethyl)aniline was found to be a suitable monodentate transient directing group (MonoTDG) to enable Ru(II)-catalyzed intermolecular direct ortho-C(sp(2))-H imidation of benzaldehydes. N-Tosyloxyphthalimide was used as an alternative azide-free amidation reagent to achieve high efficiency and good functional group tolerance. Moreover, the reaction could be enlarged to gram scale, and the amidated product could be readily converted into useful quinazoline and fused isoindolinone scaffolds by one-step derivatization.

Automated summary

2-Fluoro-5-(trifluoromethyl)aniline is a suitable MonoTDG for enabling Ru(II)-catalyzed ortho-C(sp(2))-H imidation of benzaldehydes. N-Tosyloxyphthalimide serves as an alternative amidation reagent, allowing for high efficiency and good functional group tolerance. The reaction can be scaled up to gram scale and the amidated product can be easily converted into valuable scaffolds with one-step derivatization.