Stereoselective Synthesis of Oxazolidin-2-ones via an Asymmetric Aldol/Curtius Reaction: Concise Total Synthesis of (−)-Cytoxazone

Abstract

Herein, we are reporting an efficient approach toward the synthesis of 4,5-disubstituted oxazolidin-2-one scaffolds. The developed approach is based on a combination of an asymmetric aldol and a modified Curtius protocol, which uses an effective intramolecular ring closure to rapidly access a range of oxazolidin-2-one building blocks. This strategy also permits a straightforward and concise asymmetric total synthesis of (−)-cytoxazone. Consisting of three steps, this is one of the shortest syntheses reported to date. Ultimately, this convenient platform would provide a promising method for the early phases of drug discovery.

Keywords

• oxazolidin-2-one
• (−)-cytoxazone
• natural product
• total synthesis
• curtius reaction
• asymmetric aldol