Desymmetrization of Inert -Diethers through Copper-Catalyzed Asymmetric Allylic Alkylation with Grignard Reagents.

We have developed a highly regio-, diastereo-, and enantioselective Cu-catalyzed desymmetrization of inert -diethers using Grignard reagents. Moreover, previous inaccessible sterically hindered organometallic reagents are realized in the reaction with broad secondary alkyl Grignard reagents. Finally, detailed control experiments and density functional theory calculations revealed the desymmetrization of -diethers exploits a direct -S2' pathway, in the absence of an -generated allyl bromine intermediate. The following oxidative addition is the crucial rate-determining and enantioselectivity-determining step.