A convergent synthesis of methylenomycin B and analogues via selenium assisted cyclopenta-annelation

Abstract

Reaction of the lithium enolate of 4-chloro-4,5-dimethylhex-5-en-3-one 2 with benzeneselenenyl bromide at –78 °C gives 2,3,5-trimethyl-5-phenylselenocyclopent-2-enone 3. Treatment of compound 3 with 15% H₂O₂ in methylene dichloride at 0 °C gave methylenomycin B via syn selenoxide elimination. Similarly, the lithium enolate of 7 reacted with benzeneselenenyl bromide to give 2,3-dimethyl-5-phenylselenocyclopent-2-enone 10. Compound 10 can be converted into compound 3via alkylation of its lithium enolate with methyl iodide. The lithium enolate of compound 2 also reacted with benzenesulphenyl chloride and benzoyl chloride to give 2,3,5-trimethyl-5-phenylthiocyclopent-2-enone 13 and 5-benzoyl-2,3,5-trimethylcyclopent-2-enone 14 respectively. Using this cyclization other methylenomycin B analogues were prepared from readily available starting materials.