Isoinversion Behavior in the Enantioselective Oxidations of Pyridylmethylthiobenzimidazoles to Chiral Proton Pump Inhibitors on Titanium Salalen Complexes

The oxidation of two pyridylmethylthiobenzimidazoles to proton pump inhibitors (S)-omeprazole and (R)-lansoprazole, and to their enantiomers, with H2O2 is achieved by using chiral titanium salalen complexes as catalysts. The latter ensure high enantioselectivities (up to 96% ee) and efficiencies (TN 200–300), with high sulfoxide yields (up to >96%). The oxidation enantioselectivities vary with temperature in a nonmonotonic manner, demonstrating isoinversion behavior. Maximum enantioselectivity is attained at 273···283 K, which temperature region may be recommended for preparative oxidations. Kinetic peculiarities and the oxidation mechanism are discussed.