Enantioselective Friedel-Crafts alkylation of indole with nitroalkenes in the presence of bifunctional squaramide organocatalysts

A series of chiral bifunctional quinine and 2-aminoDMAP based squaramide organocatalysts are evaluated in Friedel-Crafts alkylation of indoles with nitroolefins. These 3-substituted indole derivatives are synthesized in the presence of sterically encumbered tert-butyl squaramide/quinine with high enantioselectivity (up to >99% ee) and moderate chemical yields (up to 80%) by representing as chiral precursors for very important biologically active molecules. Besides, this asymmetric transformation provides a very simple, efficient, clean and environmental friendly route. In addition, this process has very mild reaction conditions such as ambient temperature and usage of only 2 mol% catalyst loading compared to previous studies in literature. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

A series of chiral bifunctional squaramide organocatalysts were evaluated for their application in Friedel-Crafts alkylation of indoles, showing high enantioselectivity and moderate yields. This new asymmetric transformation provides a simple, efficient, clean, and environmentally friendly route for chemical synthesis.