| The transition metal-catalyzed allylic substitution provides a powerful cross coupling reaction for the stereoselective construction of adjacent stereogenic centers. Although the enantioselective variant has dominated the chemical literature, there remain significant challenges, particularly controlling regio- and diastereocontrol in unsymmetrical allyl fragments. We have developed a stereospecific allylic substitution with ketone enolates that proceeds with excellent regio- and diastereocontrol. Additional work focused on the elucidation of the reactive metal complex, which provided the insight to develop a new chiral rhodium-complex that facilitates the highly enantioselective rhodium-catalyzed allylic substitution reaction. The combination of this transformation with a bismuth-mediated hetero-conjugate addition provides a new method for the construction of syn-1,3-polyols that are present in the biologically important natural product. The scope and limitations of these transformations and application to the marine natural product, marinomycin A will be presented. |
