Phosphine mediated (3 + 2) cycloaddition of electron-poor terminal alkynes: a concise route to pre-methylenomycin C lactone.

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 alkyne slow addition to avoid undesired alkyne deprotonation. Application to the synthesis of pre-methylenomycin C lactone, an inter-mediate in methylenomycin biosynthesis with potent activity against Gram-positive bacteria, demonstrates the robust nature and good scalability of the reaction.