General Construction of Asymmetric Amine Ethers via Efficient Transesterification

A novel method to prepare asymmetric amine ether is reported. Tertiary amine alcohol hydrogen sulfate intermediates are prepared through a reactive distillation process, followed by the transesterification process to afford eventually asymmetric amine ethers. Experiments and DFT calculations revealed the essential roles the moderately acidic sulfate group plays in the highly selective monoesterification process. This clean method is tolerant towards various functional groups with good yields under relatively rather short reaction time mild condition, which is obviously superior compared to the conventional processes.