This study reports a regiodivergent ring-expansion strategy to convert oxindoles into quinolinones, enabling the synthesis of two regioisomers from a common starting material. The method involves two distinct reaction conditions that allow for the transformation of oxindoles into quinolinone isomers. The approach is compatible with a variety of functional groups, facilitating the late-stage diversification of bioactive oxindoles and the synthesis of quinolinone drugs and their derivatives. The reaction enables the synthesis of quinolinones from oxindoles through a mechanism involving the formation of an intermediate isocyanate, followed by cyclization to yield the desired product. The method was tested with various oxindole derivatives, including those with electron-donating and electron-withdrawing groups, and was shown to be effective for the synthesis of quinolinones from biologically active oxindoles. The reaction was also applied to the synthesis of a quinolinone drug and its regioisomer, demonstrating the method's utility in drug discovery and structure-activity relationship studies. The study highlights the importance of developing new methodologies for the synthesis of regioisomers, which are crucial for the discovery of novel pharmaceuticals and other purpose-driven compounds. The findings demonstrate the potential of this method for the efficient synthesis of quinolinone derivatives and their application in drug discovery.This study reports a regiodivergent ring-expansion strategy to convert oxindoles into quinolinones, enabling the synthesis of two regioisomers from a common starting material. The method involves two distinct reaction conditions that allow for the transformation of oxindoles into quinolinone isomers. The approach is compatible with a variety of functional groups, facilitating the late-stage diversification of bioactive oxindoles and the synthesis of quinolinone drugs and their derivatives. The reaction enables the synthesis of quinolinones from oxindoles through a mechanism involving the formation of an intermediate isocyanate, followed by cyclization to yield the desired product. The method was tested with various oxindole derivatives, including those with electron-donating and electron-withdrawing groups, and was shown to be effective for the synthesis of quinolinones from biologically active oxindoles. The reaction was also applied to the synthesis of a quinolinone drug and its regioisomer, demonstrating the method's utility in drug discovery and structure-activity relationship studies. The study highlights the importance of developing new methodologies for the synthesis of regioisomers, which are crucial for the discovery of novel pharmaceuticals and other purpose-driven compounds. The findings demonstrate the potential of this method for the efficient synthesis of quinolinone derivatives and their application in drug discovery.