Enantioselective synthesis of oseltamivir phosphate

The key steps in the enantioselective synthesis of Tamiflu include an asymmetric Diels–Alder reaction, Mitsunobu inversion using Fukuyama modified Weinreb reagent, carbamate directed epoxidation. Epoxide opening with trimethylsilyl azide furnished a 3:1 mixture of regioisomers that converged to afford the same aziridine. Attempted preparation of the unsaturated ester regioselectively using 2-iodoxybenzoic acid (IBX) following Nicolaou’s protocol failed. The unsaturated ester was prepared by phenylselenylation followed by selenoxide elimination.