Multistep Continuous-Flow Synthesis of (–)-Oseltamivir
Received: 23 August 2016
Accepted after revision: 29 September 2016
03 November 2016 (eFirst)
Dedicated to Professor Dieter Enders on the occasion of his 70th birthday
A continuous-flow synthesis of (–)-oseltamivir composed of five flow units was accomplished. In each unit, the following reactions proceed efficiently: (1) a diphenylprolinol silyl ether mediated Michael reaction, (2) a domino reaction of Michael and intermolecular Horner–Wadsworth–Emmons reactions, (3) protonation, (4) epimerization, and (5) reduction of a nitro group to an amine. (–)-Oseltamivir was obtained in 13% total yield through a single flow with a residence time of 310 minutes.