Synthesis of (S)-Imperanene by Using Allylic Substitution

Synthesis of (S)-imperanene (1) was studied by using copper-assisted allylic substitution of ArCH=CHCH(L)CH(2)Ar (L: leaving group) and (i-PrO)Me(2)SiCH(2)MgCl. Preliminary substitution between PhCH=CHCH(L)Me (L = AcO, PivO, MeOCO(2), (2-Py)CO(2)) and Bu copper reagents derived from BuMgX (X = Br, Cl) and CuBr.Me(2)S or CuCl in 1:1-40:1 ratios suggested acetate 28 as the best substrate. To prepare 28, kinetic resolution of racemic (E)-TMSCH=CHCH(OH)CH(2)Ar(2) (Ar(2) = (p-TBSO)(m-MeO)C(6)H(3)) carried out by using the asymmetric epoxidation with (-)-DIPT afforded the corresponding epoxy alcohol and (S)-allylic alcohol. After separation by chromatography, these products were converted to (S,E)-Bu(3)SnCH=CHCH(OH)CH(2)Ar(2), which upon palladium-catalyzed coupling with Ar(2)-I followed by acetylation gave 28 (95-98% ee). Substitution of 28 with (i-PrO)Me(2)SiCH(2)MgCl and CuBr.Me(2)S in a 4:1 ratio at 0 degrees C proceeded cleanly to produce 29 with 100% inversion in 92% yield. Finally, Tamao oxidation furnished 1.