Ligand-Boosted Copper Catalysis for Air-Tolerant Methoxylation of (Hetero)aryl Halides With Sodium Methoxide

An air-tolerant, simple yet highly efficient copper-catalyzed methoxylation of (hetero)aryl bromides and some activated chlorides has been developed by using copper(II) chloride/2,2-bipyridine as catalyst precursor. A wide range of (hetero)aryl bromides and electron-deficient chlorides could be efficiently methoxylated in good to excellent yields at 1-mol% catalyst loading albeit showing a functional group compatibility dependent on the electronic properties of aryl ring. Applications of the practical protocol have been demonstrated in multigram synthesis of 3,4,5-trimethoxytoluene.