Time Economical Total Synthesis of (−)-Oseltamivir

A time economical 60 min total synthesis of (−)-oseltamivir was accomplished in a single reaction vessel over five steps. One of the key issues is reduction in the number of steps by eliminating lengthy reaction steps with substitution of a rapid epimerization step. A catalytic system consisting of three reagents, namely, diphenylprolinol silyl ether, thiourea, and acid, was developed for a rapid asymmetric Michael reaction with excellent diastereo- and enantioselectivities. All reactions were optimized in terms of not only yield and selectivity but also reaction time.