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]

Mechanism

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Related Reactions

Related Compounds