Synthesis of Halomethyl and Other Bipyridine Derivatives by Reaction of 4,4‘-Bis[(trimethylsilyl)methyl]-2,2‘-bipyridine with Electrophiles in the Presence of Fluoride Ion

Bipyridine (bpy) ligands figure prominently in many areas of chemistry. Common precursors to many derivatives are the halomethyl-substituted analogues. This report describes a new, high yield route to these valuable compounds via a trimethylsilyl (TMS) intermediate. 4,4‘-Dimethyl-2,2‘-bpy was reacted with lithium diisopropylamide, and the dianion thus formed was trapped with TMSCl to generate 4,4‘-bis[(trimethylsilyl)methyl]-2,2‘-bpy (1). The TMS group was removed using dry F- sources (TBAF/SiO2 in THF or CsF in DMF) in the presence of BrF2CCF2Br or Cl3CCCl3 to produce the bromide 2 or chloride 3 analogues of 4,4‘-bis(halomethyl)-2,2‘-bipyridine, respectively. The CsF/DMF methodology extends to other electrophiles, including benzaldehyde to give 4,4‘-bis(2-hydroxy-2-phenethyl)-2,2‘-bpy, 6, as well as to alkyl halides. Benzyl Br, dodecyl Br, and α-chloroacetonitrile gave mixtures of di- and monoalkylated products along with the diprotonated product, 4,4‘-dimethyl-2,2‘-bpy.