Phosphine-Mediated (3 + 2) Cycloaddition of Electron-Poor Terminal Alkynes: A Concise Route to Premethylenomycin C Lactone.

Abstract

Herein, we report a (3 + 2) cycloaddition to deliver an array of cyclopentenes. Typically, the reaction involves electron-poor terminal alkynes and ketomalonate partners; however, numerous structural modifications to the coupling partners have been accommodated to enable 45 examples of the reaction to be completed. Mechanistic studies highlight the role of slow alkyne addition to avoid undesired alkyne deprotonation. Application to the synthesis of premethylenomycin C lactone, an intermediate in methylenomycin biosynthesis with potent activity against Gram-positive bacteria, demonstrates the robust nature and good scalability of the reaction.