Nickel-Catalyzed Chemo- and Diastereoselective Dearomative Dialkylation of Indoles with Two Different Alkyl Halides

The catalytic dearomative dicarbofunctionalization of indoles constitutes one of the most efficient ways to access poly-substituted indolines that are prevalent in many natural products and drugs. However, despite significant advances, three component dearomative dicarbofunctionalization of indoles has remained elusive. Herein, we report an unprecedented nickel-catalyzed dearomative dialkylation of indoles with two different alkyl halides via three component cross-electrophile coupling under mild conditions with the construction of two vicinal C(sp³)─C(sp³) bonds at C2 and C3 sites. The catalytic protocol offers an efficient and straightforward route for the modular assembly of diverse carbon quaternary center-containing dialkylated indoline derivatives with a broad substrate scope (75 examples), excellent functional group tolerance and high chemo- and diastereoselectivities. Mechanistic studies, combining a series of experiments and DFT calculations, reveal that the catalytic reaction proceeds via a radical pathway.