Totally Synthetic by Paul H. Docherty, 4 May 2006

Total Synthesis of Oseltamivir phosphate (Tamiflu)

Shibasaki

Y. Fukuta, T. Mita, N. Fukuda, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2006, 128, 6312-6313.

DOI: 10.1021/ja061696k

Shibasaki’s synthesis of Tamiflu is published on the same day as Corey's. This nitrogen-rich route employs an enantioselective ring-opening of meso-aziridines with azide, leading to anti addition of nitrogen.

Using this impressive methodology, they construct the first intermediate in the scheme below, and convert to a meso diamide in five steps. The C₂ symmetry was then lost by SeO₂ allylic oxidation, generating the next intermediate. Addition of cyanide and asymmetric reduction generated the final stereocenter, and allowed completion of the synthesis in seven further steps.