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Synfacts 2025; 21(07): 712
DOI: 10.1055/a-2606-8207
Metals in Synthesis

Tin-Free Palladium-Catalyzed Coupling of Secondary Amines with Aryl Bromides

Contributor(s):
Mark Lautens 
,
Andrew G. Durant
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
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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.


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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.


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Publication History

Article published online:
23 June 2025

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