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.
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