CYCLOPROPANATION REDUCTION OF A 3,4-DISUBSTITUTED 2(5H)-FURANONE - A MODEL FOR C-8 METHYLATION AT THE TAXANE BC RING JUNCTURE/

A cyclopropanation/reduction strategy is described that should prove u seful for incorporation of the C-8 methyl group at the taxane BC ring juncture. Treatment of model 2(5H)-furanone 6 with various organocoppe r-based reagents resulted in gamma-deprotonation to the furan oxide ra ther than the desired conjugate addition. This pathway was established by deuteration studies. Reaction of 6 with dimethylsulfoxonium methyl ide in DMSO at room temperature also led exclusively to gamma-deproton ation; however, the use of excess methylide at 50 degrees C led to the clean formation of the desired cyclopropanated adduct 13. While the c yclopropane ring in 13 proved resistant to various heterogeneous hydro genation conditions, treatment with Li/liq NH3 under careful;temperatu re control(-78 degrees C to -63 degrees C) led to the regioselective f ormation of the desired ring-opened product 7 with high (16:1) diaster eoselectivity.