Hydrated ferric sulfate-catalyzed reactions of indole with aldehydes, ketones, cyclic ketones, and chromanones: Synthesis of bisindoles and trisindoles. Issue 27 (6th July 2017)

• Record Type: Journal Article
• Authors: Noland, Wayland E.; Kumar, Honnaiah Vijay; Flick, Grant C.; Aspros, Cole L.; Yoon, Jong Hyeon; Wilt, Andre C.; Dehkordi, Nasim; Thao, Sheng; Schneerer, Andrew K.; Gao, Siming; Tritch, Kenneth J.
• Is Part Of: Tetrahedron. Volume 73:Issue 27/28(2017)
• Page Start: 3913
• Page End: 3922
• Publication Date: 2017-07-06
• Subjects: Ferric sulfate -- Bisindole -- Trisindole -- Chromanone -- Cyclic ketone -- Aldehyde; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2017.05.061
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Hydrated ferric sulfate [Fe2 (SO4 )3 · x H2 O] has been found to be an efficient catalyst for condensation of bisindoles or trisindoles with aliphatic or aryl aldehydes and ketones including methyl and ethyl-alkyl ketones, methyl aryl ketones, cyclic ketones, and 4-chromanones in 19–96% yields. Trisindoles and 2, 2'-alkylidenebisindoles were obtained from indole-3-carbaldehydes or 3-methylindole in 72–84% yields. A total of 43 substrates was employed, giving 33 bisindoles, 3 trisindoles, and one 2:2 product; seventeen of these are new. The best results were obtained from heating ethanolic suspensions, with Fe2 (SO4 )3 · x H2 O loaded at 60 mg per mmol of electrophiles. The reaction times were typically 1–4 h, while hindered electrophiles required 8–24 h. These conditions were strong enough to promote 2:1 condensation of indole with substrates without forming higher-order byproducts, with few exceptions. This strategy features tolerance by the catalyst of a wide range of functional groups, readily available starting materials, simple operation, mild reaction conditions, and is environmentally friendly. Graphical abstract: Highlights: Hydrated ferric sulfate is an efficient catalyst to access bisindoles and trisindoles. The scope of the use of the catalyst is explored, and includes cyclic ketones and chromanones. Initial screenings for the antioxidant potentials of chromanone-derived bisindoles are promising. Preliminary results of antitumor testing performed by the National Institutes of Health were also promising.