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

Abstract

Mixed TMP-bases (TMP=2,2,6,6-tetramethylpiperidyl), such as TMPMgCl ⋅ LiCl, TMP2Mg ⋅ 2LiCl, TMPZnCl ⋅ LiCl and TMP2Zn ⋅ 2LiCl, are outstanding reagents for the metalation of functionalized aromatics and heterocycles. In the presence of Lewis acids, such as BF3 ⋅ OEt2 or MgCl2, 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 Cy2NLi, are also compatible with various Lewis acids, such as MgCl2 ⋅ 2LiCl, ZnCl2 ⋅ 2LiCl or CuCN ⋅ 2LiCl. Performing such metalations in continuous flow using commercial setups permitted practical and convenient reaction conditions.