Enantioselective Friedel–Crafts Alkylation of Indoles with β,γ-Unsaturated α‑Ketoesters Catalyzed by New Copper(I) Catalysts

• Published in: Journal of organic chemistry 2023-03, Vol.88 (5), p.3046-3053
• Main Authors: Yu, Shibo, Cai, Qihang, Wang, Chao, Hou, Jiaqi, Liang, Jiemian, Jiao, Zilin, Yao, Chao, Li, Yue-Ming
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c02749

New Cu­(I) catalysts are effective in enantioselective Friedel–Crafts alkylation of a variety of indoles with different β,γ-unsaturated α-ketoesters. A control study shows that such a catalyst system is less sensitive to air, and the reactions can be carried out without special cares such as glovebox operation or moisture/oxygen-free conditions. Preliminary computation results suggest that there exists π–π stacking between the substrate and the catalyst, and such an interaction seems to play a role in stabilizing the reaction intermediate and enhancing the stereoselectivity of the reactions. The desired products can be obtained in up to 98% yield at 99% enantiomeric excess. The same high enantioselectivity can be observed when the reaction is carried in a gram scale, indicating a good scalability of the catalyst system in enantioselective Friedel–Crafts alkylation of different indoles with β,γ-unsaturated α-ketoesters.