Synthesis of CF 3 -Isoquinolinones and Imidazole-Fused CF 3 -Isoquinolinones Based on C-H Activation-Initiated Cascade Reactions of 2-Aryloxazolines.

Presented herein are novel syntheses of CF 3 -isoquinolinones and imidazole fused CF 3 -isoquinolinones based on the cascade reactions of 2-aryloxazolines with trifluoromethyl imidoyl sulfoxonium ylides. The formation of CF 3 -isoquinolinone involves an intriguing cascade process including oxazolinyl group-assisted aryl alkylation through C(sp 2 )-H bond metalation, carbene formation, migratory insertion, and proto-demetalation followed by intramolecular condensation and water-promoted oxazolinyl ring-scission. With this method, the isoquinolinone scaffold tethered with valuable functional groups was effectively constructed. By taking advantage of the functional groups embedded therein, the products thus obtained could be readily transformed into imidazole-fused CF 3 -isoquinolinones or coupled with some clinical drugs to furnish hybrid compounds with potential applications in drug development. In general, the developed protocols feature expeditious and convenient formation of valuable CF 3 -heterocyclic skeletons, broad substrate scope, and ready scalability. In addition, studies on the activity of selected products against some human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.