Synthesis of Quinolines and 2-Functionalized Quinolines by Difluorocarbene Incorporation

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 alpha-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 H2Se 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.