Divergent Synthesis of CF ₃ ‐Spiro[Benzoxazine‐Isoquinolines] and CF ₃ ‐Isoquinolinones via Controllable Rh(III)‐Catalyzed C─H Spirocyclization

A condition‐tunable Rh(III)‐catalyzed divergent synthetic strategy toward CF 3 ‐spiro[benzoxazine‐isoquinolines] and CF 3 ‐isoquinolinones from readily available 3‐arylbenzoxazines and CF 3 ‐imidoyl sulfoxonium ylides has been established. Specifically, when the reaction was performed in DCM under an air atmosphere with NaOAc as the additive, CF 3 ‐spiro[benzoxazine‐isoquinolines] were obtained through a C─H activation‐initiated [3 + 3] spirocyclization process. In contrast, employing Cu(OAc) 2 /PivOH as co‐additives in DCE with a small amount of H 2 O under an oxygen atmosphere enabled the formation of CF 3 ‐substituted isoquinolinones, which proceeded via C─H [3 + 3] spirocyclization followed by directing group detachment through C─C/C─N bond cleavage. To the best of our knowledge, this work constitutes the first report on the use of benzoxazines as directing groups to promote C─H functionalization with the spontaneous detachment of the directing group. Notably, in vitro antitumor activity evaluations demonstrated that several synthesized products exhibit excellent antiproliferative effects against several cancer cell lines.