Allylic C-H oxygenation of unactivated internal olefins by the Cu/azodiformate catalyst system

Allylic ethers and alcohols are essential structural motifs commonly present in natural products and pharmaceuticals. Direct allylic C-H oxygenation of internal alkenes is one of the most direct methods, bypassing the necessity for an allylic leaving group that is needed in the traditional Tsuji-Trost reaction. Herein, we develop an efficient and practical method for synthesizing (E)-allyl ethers from readily available internal alkenes and alcohols or phenols via selective allylic C-H oxidation. Key advances include the use of a Cu/Azodiformate catalyst system to facilitate remote allylic C-H activation and the achievement of excellent chemoselectivity through a dynamic ligand exchange strategy using a bis(sulfonamide) ligand. This method features a broad substrate scope and functional group tolerance, successfully applied to the synthesis of various challenging medium-sized cyclic ethers (7-10 members) and large-ring lactones (14-20 members), with high regioselectivity and stereoselectivity.