Louie J,
Hartwig JF *.
Yale University, New Haven, USA
Palladium-Catalyzed Synthesis of Arylamines from Aryl Halides. Mechanistic Studies
Lead to Coupling in the Absence of Tin Reagents.
Tetrahedron Lett. 1995;
36: 3609-3612
DOI:
10.1016/0040-4039(95)00605-C
Keywords
palladium - cross-coupling - amines - aryl bromide
Significance
Three decades ago, Hartwig (shown) and Buchwald (Angew. Chem., Int. Ed. Engl.
1995, 34, 1348) reported tin-free cross-couplings of secondary amines with aryl halides under
palladium catalysis. Previously this reaction required tin amides which are air- and
moisture-sensitive and create stoichiometric tin halide byproducts. Thorough mechanistic
investigations enabled the Hartwig group to remove this requirement, allowing them
to make strides toward simplifying one of the most commonly used reactions.
Comment
Mechanistic studies indicated to the Hartwig group that the resting state of the palladium
catalyst when using tri-o-tolylphosphine as a ligand is the dimeric PdII oxidative addition species. They also showed that this complex could be cleaved by
an amine acting as an L-type ligand. The increased acidity of the coordinated amine
allows for deprotonation by the base making it an X-type ligand. Reductive elimination
furnishes the coupled product.
