Synfacts 2018; 14(11): 1109
DOI: 10.1055/s-0037-1609630
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Oseltamivir Phosphate

Philip Kocienski
Li H, Shen S.-J, Zhu C.-L, Xu H. * Georgia State University, Atlanta, USA
Enantioselective Synthesis of Oseltamivir Phosphate (Tamiflu) via the Iron-Catalyzed Stereoselective Olefin Diazidation.

J. Am. Chem. Soc. 2018;
140: 10619-10626
Further Information

Publication History

Publication Date:
18 October 2018 (online)



Xu and co-workers report a gram-scale synthesis of the neuraminidase inhibitor ­oseltamivir phosphate (Tamiflu®), in which the trans-diamino moiety was installed through an iron-catalyzed, diastereoselective diazidation of enantiopure olefin E to give the 1,2-trans-diazide H in 70% yield (dr > 20:1). Electronically deactivated substrates, that have been otherwise problematic, are tolerated.



Mechanistic studies revealed that both the iron catalyst and the complex substrate cooperatively modulate the stereoselectivity of the di­azidation. Process safety assessment using both differential scanning calorimetry and the drop weight test indicate that the diazidation reaction can be performed on large scale.