Synthesis of Continuously Substituted Quinolines from o-Alkenyl Aromatic Isocyanides by Palladium-Catalyzed Intramolecular Imidoylative 6-endo Cyclization

Abstract

An efficient synthesis of continuously substituted quinoline derivatives via palladium-catalyzed intramolecular 6-endo imidoylative cyclization of o‐alkenyl aryl isocyanides with (hetero)aryl halides or vinylic triflates has been developed. The reaction proceeds through the concerted metalation-deprotonation (CMD) mechanism by activation of vinyl C-H bond with imidoylpalladium assisted by the carboxylate. Quinoline as an important heterocyclic scaffold, is prevalently found in natural products, biologically active molecules and functional materials,1 and is also a useful synthon in organic synthesis.2 Thus, various synthetic methods for quinoline motifs have been developed. Representative approaches include condensation reactions3 and catalyzed addition/cyclization approaches.4 Despite these advances, there remains big demand for versatile and effective methodologies to regioselective construct multiple substituted quinoline motifs. Aryl isocyanides have been well exploited in the preparation of nitrogen-containing heterocycles.5 In this context, alkene-containing isocyanides have received much attention, because they can be easily tuned in a way to synthesize a plethora of N-heterocyclic derivatives.6 Takahashi et al reported a three-component coupling reaction of o-alkenylphenyl isocyanides with aryl iodides and amines in the presence of palladium catalyst to produce 2,3-substituted indoles (Figure 1).6a Zhu group reported synthesis of five- to seven-membered cyclic ketoimines through palladium-catalyzed intramolecular imidoylative Heck reaction of alkene-containing isocyanides.6b Wang et al reported the palladium-catalyzed reaction of alkene-containing isocyanides with N-(2-bromobenzoyl)indoles via