Development of New Synthetic Methodology Based on Zirconium-Mediated Carbon-Carbon Bond Forming Reaction

Zirconium-mediated carbon-carbon bond forming reactions have been extensively developed for the last decade. An allylic zirconium species and related organozirconium species can be prepared from the reaction of allylic ethers with zirconocene equivalent “Cp2Zr” through β-alkoxide elimination under mild conditions. This methodology is applicable to the ring contraction reaction of vinyl sugar and vinyl morpholine derivatives to give enantiomerically pure polyfunctionalized carbocycles and pyrrolidines with high diastereoselectivity, respectively. The origin of high diastereoselectivity in these transformations was deduced by isolating the nine-membered cyclic intermediate possessing (Z) -allylic zirconium species. Useful applications of this zirconium-mediated ring contraction reaction to syntheses of bioactive compounds are also described. It is also discussed that the diastereoselectivity of the zirconium-mediated coupling reaction of a chiral imine with unsaturated compounds is highly dependent on the generating temperature of zirconacycles.