Cyclopropanation/Reduction of a 3,4-Disubstituted 2(5<i>H</i>)-Furanone: A Model for C-8 Methylation at the Taxane BC Ring Juncture

Abstract

A cyclopropanation/reduction strategy is described that should prove useful for incorporation of the C-8 methyl group at the taxane BC ring juncture. Treatment of model 2(5H)-furanone 6 with various organocopper-based reagents resulted in γ-deprotonation to the furan oxide rather than the desired conjugate addition. This pathway was established by deuteration studies. Reaction of 6 with dimethylsulfoxonium methylide in DMSO at room temperature also led exclusively to γ-deprotonation; however, the use of excess methylide at 50 °C led to the clean formation of the desired cyclopropanated adduct 13. While the cyclopropane ring in 13 proved resistant to various heterogeneous hydrogenation conditions, treatment with Li/liq NH3 under careful temperature control (−78 °C to −63 °C) led to the regioselective formation of the desired ring-opened product 7 with high (16:1) diastereoselectivity.