Synthesis of Oseltamivir Phosphate

Key words

oseltamivir phosphate - neuraminidase inhibitor - olefin diazidation - iron catalysis - vicinal diazides - 1,2-trans-diamines

Significance

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.

Comment

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.