Regioselective Magnesiation and Zincation Reactions of Aromatics and Heterocycles Triggered by Lewis Acids

Mixed TMP‐bases (TMP=2,2,6,6‐tetramethylpiperidyl), such as TMPMgCl ⋅ LiCl, TMP(2)Mg ⋅ 2LiCl, TMPZnCl ⋅ LiCl and TMP(2)Zn ⋅ 2LiCl, are outstanding reagents for the metalation of functionalized aromatics and heterocycles. In the presence of Lewis acids, such as BF(3) ⋅ OEt(2) or MgCl(2), the metalation scope of such bases was dramatically increased, and regioselectivity switches were achieved in the presence or absence of these Lewis acids. Furthermore, highly reactive lithium bases, such as TMPLi or Cy(2)NLi, are also compatible with various Lewis acids, such as MgCl(2) ⋅ 2LiCl, ZnCl(2) ⋅ 2LiCl or CuCN ⋅ 2LiCl. Performing such metalations in continuous flow using commercial setups permitted practical and convenient reaction conditions.