Abstract:
Elbasvir and ruzasvir are the NS5A protein inhibitor in Merck’s oral combination therapy for the treatment of hepatitis C. The aminal stereocenter of elbasvir was efficiently constructed by a novel Pd-catalyzed asymmetric intramolecular C-N coupling. This transformation has been shown to be general for a wide variety of N,O- and N,N-acetals. Mechanistic studies revealed the active ligand to be a diphosphine monoxide. This presentation will discuss the discovery, optimization, scope, and mechanstic insights of the asymmetric aminal synthesis.