Design, Synthesis and Anticancer Evaluation of Novel SO2F-Containing Medicinally Privileged Structures via Ketone-Directed C-H Functionalization.

The weakly coordinating ketone group-directed C-H functionalizations of chromones, flavones, 1,4-naphthoquinones, (thio)xanthones, and acridones with ethenesulfonyl fluoride under rhodium(III) or ruthenium(II) catalysis are described. These protocols efficiently provide a range of chromone-based scaffolds and xanthone analogues bearing an SO2F group with excellent site-selectivity and functional group compatibility. The practicality of this approach was demonstrated by simple SuFEx conjugations with representative biologically relevant molecules, DNA conjugation, and Michael addition with a secondary amine. All the synthesized derivatives were initially screened for their in vitro cytotoxic activity against human lung adenocarcinoma A549 cells. In particular, compound 5aa with a xanthone scaffold was found to be highly cytotoxic.