Synthesis of ( R )-Modafinil via Organocatalyzed and Non-Heme Iron-Catalyzed Sulfoxidation Using H 2 O 2 as an Environmentally Benign Oxidant

摘要

The first organocatalyzed sulfoxidation reaction towards enantioenriched ( R )-modafinil (Armodafinil ? ), a drug against narcolepsy, is reported here. A series of chiral organocatalysts, e.g., different chiral BINOL-phosphates, or a fructose-derived N- substituted oxazolidinone ketone (Shi catalyst) were applied for the sulfoxidation reaction with environmentally friendly H 2 O 2 as a convenient oxygen transferring agent. Furthermore, the potential of a biomimetic catalytic system consisting of FeCl 3 and a dipeptide-based chiral ligand was demonstrated, which constitutes the most successful asymmetric non-heme iron-catalyzed synthesis of ( R )-modafinil so far.