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.

以过氧化氢（H₂O₂）为氧化剂，在手性salalen钛配合物（chiral titanium salalen complexes）催化下，可将两种吡啶甲基硫代苯并咪唑类化合物氧化为质子泵抑制剂（proton pump inhibitors）(S)-奥美拉唑（omeprazole）与(R)-兰索拉唑（lansoprazole）及其对映异构体。该催化剂可实现优异的对映选择性（最高可达96%对映体过量值（enantiomeric excess，ee））与催化转化效率（转化数（turnover number，TN）为200~300），亚砜产物收率最高可达96%以上。该氧化反应的对映选择性随温度呈现非单调变化规律，表现出等反转行为（isoinversion behavior），其最大对映选择性出现在273~283 K区间，该温度区间可用于制备规模的氧化反应。本文还探讨了该氧化反应的动力学特性与反应机理。