Synthesis of Esomeprazole and Related Proton Pump Inhibitors through Iron-Catalyzed Enantioselective Sulfoxidation
journal contributionposted on 2018-08-29, 00:00 authored by Shigenobu Nishiguchi, Takuhiro Izumi, Takayoshi Kouno, Junpei Sukegawa, Laurean Ilies, Eiichi Nakamura
We report here an application of iron catalysis for the kilogram scale asymmetric synthesis of a proton pump inhibitor, esomeprazole, in 87% yield and 99.4% ee by catalytic sulfoxidation with hydrogen peroxide using an iron salt/chiral Schiff base in combination with a carboxylate salt. Under similar reaction conditions, other proton pump inhibitors such as (S)-lansoprazole, (S)-rabeprazole, and (S)-pantoprazole, were also synthesized in high yield and ee. A carboxylate additive was crucial for the success of this reaction, and we consider that it coordinates to the active iron species, and it also acts as a hydrogen-bond acceptor to coordinate to the substrate through the imidazole NH.