Adaptive alcohols-alcohols cross-coupling via TFA catalysis: access of unsymmetrical ethers

Ethers are high value organic compounds widely applied in chemical industry, natural products, material, pharmaceuticals, argochemicals, as well as modern organic synthesis. Herein, we report an adaptive TFA-catalyzed cross-coupling of alcohols with various oxygen nucleophiles (nitro-, halogen-, sulfur-, nitrogen-, aryl-, and alkynyl-substituted aliphatic alcohols), delivering diverse unsymmetrical ethers under mild conditions and simple operation. This protocol features a broad range of substrate scope and high catalytic efficiency (54 examples, up to 99% yield). The decagram scale performance and one-step synthesis of drug molecules evidenced the potential industrial production and practicability of this protocol.