Stereoselective Synthesis of Baloxavir Marboxil Using Diastereoselective Cyclization and Photoredox Decarboxylation of l-Serine.

Baloxavir marboxil (1; BXM) is a potent drug used for treating influenza infections. The current synthetic route to BXM (1) is based on optical resolution; however, this method results in the loss of nearly 50% of the material. This study aimed to describe an efficient and simpler method for the synthesis of BXM. We achieved a stereoselective synthesis of BXM (1). The tricyclic triazinanone core possessing a chiral center was prepared via diastereoselective cyclization utilizing the readily available amino acid l-serine. The carboxyl moiety derived from l-serine was removed via photoredox decarboxylation under mild conditions to furnish the chiral tricyclic triazinanone core ((R)-14). The synthetic route demonstrated herein provides an efficient and atomically economical method for preparing this potent anti-influenza agent.

Switch in stereoselectivity caused by the isocyanide structure in the rhodium-catalyzed silylimination of alkynes.

The reaction of terminal alkynes with hydrosilanes and tert-alkyl isocyanides in the presence of Rh(4)(CO)(12) gives (Z)-ß-silyl-α,ß-unsaturated imines in good yields. On the other hand, the use of aryl isocyanides in place of tert-alkyl isocyanides leads to the formation of E isomers.