Stereoselective anti-SN2′-Substitutions of Secondary Alkylcopper-Zinc Reagents with Allylic Epoxides: Total Synthesis of (3S,6R,7S)-Zingiberenol

Abstract

Chiral secondary mixed alkylcopper-zinc reagents were prepared from the corresponding alkyl iodides and reacted with allylic epoxides via an anti-SN2′-substitution and retention of configuration of the chiral alkylorganometallic, leading to chiral allylic alcohols. This method was used in a total synthesis of the natural product (3S,6R,7S)-zingiberenol in 8 steps and 9.7% overall yield [dr (3S,6R) = 99:1; dr (6R,7S) = 81:19] starting from commercially available 3-methyl-2-cyclohexenone.