Dual Catalytic Synthesis of Antiviral Compounds Based on Metallocarbene–Azide Cascade Chemistry
datasetposted on 17.04.2018, 00:00 by Bren Jordan P. Atienza, Lionel D. Jensen, Sarah L. Noton, Anil Kumar Victoria Ansalem, Tom Hobman, Rachel Fearns, David J. Marchant, F. G. West
Aryl azides trap ortho-metallocarbene intermediates to generate indolenones possessing a reactive C-acylimine moiety, which can react with added indole nucleophiles to afford the 2-(3-indolyl)indolin-3-one scaffold found in the antiviral natural product isatisine A. This overall process occurs through a dual catalytic sequence at room temperature. Redox activation of the Cu(OTf)2 precatalyst by indole results in catalytically competent Cu(I) required for azide–metallocarbene coupling. The Brønsted acid that is also formed from Cu(OTf)2 reduction is responsible for catalysis of the C–C bond-forming indole addition step. This modular, procedurally simple method allows for rapid assembly of bis(indole) libraries, several of which proved to have anti-infective activity against respiratory syncytial virus and Zika virus.