Accessing Antitumor Anilino-1-Indolinones via Bronsted Acid-Catalyzed para –C–H Aminoalkylation of Anilines with 3-Hydroxyisoindolinones

We report the efficient synthesis of anilino-1-indolinone derivatives via the highly regioselective para–C–H aminoalkylation of anilines with 3-hydroxyisoindolinones. This reaction proceeds rapidly in the presence of 1,1′-Binaphthyl-2,2′-diyl hydrogen phosphate (BNDHP) as a Bro̷nsted acid catalyst. The versatile transformation and good anticancer activities of the obtained anilino-isoindolinone derivatives further demonstrated their practicality. The possible regulatory signaling pathways and potential targets of the antitumor effects of anilino-isoindolinone derivatives were studied preliminarily through network pharmacology, molecular docking, and molecular dynamics simulations. DFT calculations provide a detailed understanding of the high chemoselectivity of this reaction.