Synthesis Of Quinolin-2(1H)-one Derivatives Via Tandem Reaction

As a "privileged" scaffold, quinolin-2(1H)-one and its derivatives are ubiquitous subunits of numerous natural products, as well as extremely important class of heterocycles due to their wide applications in the areas of medicinal chemistry. Meanwhile, it is well known that the tandem reaction is one of the high efficient strategies that could generate small molecules with structural diversity and complexity. This thesis is mainly focused on the tandem reactions for the generation of quinolin-2(1H)-one derivatives.Firstly, we have developed two efficient approaches to construct biologically important 3H-pyrrolo[2,3-c]quinolin-4(5H)-one and thieno[2,3-c]quinolin-4(5H)-one derivatives from the readily available 4-alkynyl-3-bromoquinolin-2(1H)-one as precursor by the domino process. Palladium-catalyzed domino reaction of 4-alkynyl-3-bromoquinolin-2(1H)-one with amine provided a practical synthesis of highly functionalized 3H-pyrrolo[2,3-c]quinolin-4(5H)-ones in good yields. While thieno[2,3-c]quinolin-4(5H)-one derivatives could be obtained via a domino substitution/cyclization process between 4-alkynyl-3-bromoquinolin-2(1H)-one and sodium hydrosulfide with good functional tolerance under mild conditions. Application of the developed method has been successfully extended for the synthesis of ningalin B and lamellarin D analogues, chromeno[3,4-b]pyrrol-4(3H)-one derivatives. These protocols provide straightforward access to more diversity in the scaffold for drug discovery and material sciences.Secondly, we have developed a straightforward and convenient method for Pd-catalyzed direct heteroarylation of electron-deficient polyfluoroarenes. The reaction makes direct use of a simple polyfluoroarenes and readily available and inexpensive heteroaromatic triflates and chlorides. This protocol provides a useful and facile access to polyfluoroaryl quinolin-2(1H)-one and coumarin derivatives.