Nickel-Catalyzed Substitution of Allylic Ethers and Acetals with Organoboroxines in the Presence of Pyrimidine

Transformations at the allylic position are ubiquitous in organic synthesis, typically proceeding under transition metal catalysis. Despite their promises of sustainability, ethers still face limited use as feedstocks for allylic substitution due to the poor leaving ability of alkoxy groups. Herein, we describe an efficient nickel-catalyzed protocol for the cross-coupling of allylic ethers with organoboroxines in the presence of a catalytic amount of pyrimidine. In particular, the Lewis acidity of the organoboroxine was proven, computationally and experimentally, to be crucial in the activation of the inert C–O bond of allylic ethers. The reaction exhibits high regio- and chemoselectivity and is stereospecific, generating linearly substituted products with an overall inversion of stereochemistry. The practicality and synthetic utility of the reaction were demonstrated through rapid transformation under relatively mild conditions and the use of only cheap and bench-stable reagents. The method can be applied to allylic acetals, where mono- and disubstitution can be precisely selected by controlling the stoichiometry. Exploiting the necessity for Lewis acidity, an unprecedented controlled sequential disubstitution of acetals by different organoboroxines was also achieved.