Efficient AIkyI Ether Synthesis via Palladium-Catalyzed, Picolinamide-Directed Alkoxylation of Unactivated C(sp~3)-H and C(sp~2)-H Bonds at Remote Positions

摘要

We report the efficient synthesis of alkyl ethers by the functionalization of unactivated sp~3- and sp~2-hybridized C-H bonds. In the Pd(OAc)_2-catalyzed, PhI(OAc)_2-mediated reaction system, picolinamide-pro-tected amine substrates undergo facile alkoxylation at the γ or δ positions with a range of alcohols, including t-BuOH, to give alkoxylated products. This method features a relatively broad substrate scope for amines and alcohols, inexpensive reagents, and convenient operating conditions. This method highlights the emerging value of unactivated C-H bonds, particularly the C(sp~3)-H bond of methyl groups, as functional groups in organic synthesis.