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(sp<sup>3</sup>)─C(sp<sup>3</sup>) 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.
Authors
- Xinmiao Huang
- Yuanhong Ma (ORCID: https://orcid.org/0000-0001-6300-6897)
- Menghao Yao
- Abing Duan (ORCID: https://orcid.org/0000-0002-9524-1493)
- Boming Shen
Institutions
- Hunan University (CN)
- Hunan Normal University (CN)
- Southern University of Science and Technology (CN)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-12-26
- DOI
- https://doi.org/10.1002/anie.202520330
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Hunan Normal University