The Buchwald-Hartwig cross-coupling reaction (Buchwald-Hartwig Amination) uses catalytic palladium and a strong base in stoichiometric amounts to make an aryl amine from an aryl halide and a 1° or 2° amine. Oxidative addition of the aryl halide to the Pd(0) catalyst occurs first, followed by amine coordination to the Pd(II) complex. A strong base assists in deprotonating the amine, nitrogen bonding to Pd(II), and displacing the halide. Reductive elimination forms the desired C-N bond and regenerates the catalyst.

  • Reagents: Catalytic Palladium, Base (NaOt-Bu, LHMDS, K2CO3, or Cs2CO3), Solvent (THF, Toluene, Dioxane)
  • Reactant: Aryl Halide/Sulfonate and 1° or 2° Aliphatic/Aromatic Amine, or Imide, Amide, Sulfonamide, Sulfoximine
  • Product: Aryl Amine
  • Type of Reaction: Cross-Coupling
  • Bond Formation: Aryl C-N

Lab Tips

  • Better yields are obtained when the Pd(0) catalyst is complexed with chelating phosphine type ligands such as BINAP, DPPF, XANTPHOS, and DPBP or bidentate ligands such as trans,trans-dibenzylideneacetone (DBA). [1]
  • The amination of aryl chlorides can be especially difficult, requiring bulky phosphines to achieve reasonable yields. [2] Solvent-free protocols have shown to be highly effective. [3]
  • Reaction temperatures range from 25 °C to over 100 °C. [1][1][1]
1. Kürti, L., Czakó, B. (2005). Strategic Applications of Named Reactions in Organic Synthesis; Background and Detailed Mechanisms. Burlington, MA: Elsevier Academic Press.
2. Dorel et al. The Buchwald-Hartwig Amination After 25 Years. Angewandte Chemie (International ed. in English) 2019, 58(48), 17118–17129.
3. Chartoire et al. Solvent-free arylamination catalysed by [Pd(NHC)] complexes. RSC Adv. 2013, 3, 3840-3843.


Top Citations

Original Paper

Related Reactions

  • Ullmann Reaction

Related Compounds

By shuhan yang


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