Practical and economic lithiations of functionalized arenes and heteroarenes using Cy2NLi in the presence of Mg, Zn or La halides in a continuous flow

Abstract

The economic amide base lithium dicyclohexylamide (Cy₂NLi) allows fast and convenient (40 s, 0 °C) in situ trapping flow metalations of a broad range of functionalized arenes, heteroarenes and acrylate derivatives in the presence of various metal salts (ZnCl₂·2LiCl, MgCl₂, LaCl₃·2LiCl). The resulting Zn-, Mg- or La-organometallic intermediates are trapped with various electrophiles in high yields. These flow metalations are easily scaled-up without further optimization.