Synthesis of Quinolines and 2‐Functionalized Quinolines by Difluorocarbene Incorporation

Abstract A general method is developed to allow de novo construction of quinolines and C2‐functionalized quinolines from ortho ‐alkenyl anilines in the presence of a difluorocarbene precursor. This method exploits a crucial reactivity of in‐situ generation of isocyanides from condensation of primary aniline with difluorocarbene. Subsequent α‐addition of isocyanide by neighbouring alkenyl group constructs the quinoline ring. Furthermore, when a combination of difluorocarbene precursor and Se are present, selenoisocyanate intermediates are tentatively generated that upon nucleophilic addition by ortho ‐alkenyl produce 2‐SeH quinolines. In the presence of a second nucleophile such as anilines, competing nucleophilic addition of anilines to the selenoisocyanate is preferred, generating selenourea intermediate. Further nucleophilic addition of the ortho ‐alkenyl to selenourea followed by elimination of H 2 Se produces 2‐aminoquinolines. This allows one‐step multi‐component modular preparation of various C2‐functionalized quinolines from readily available starting compounds. This method shows good yields, scope and chemoselectivity. It is operationally convenient and friendly without manipulating unpleasant isocyanides. The difluorocarbene‐enabled primary amine to isocyanide conversion may be exploited to develop other interesting reactions. magnified image