two different transformations referred as the Ullmann Reaction. The
"classic" Ullmann Reaction is the synthesis of symmetric biaryls via
copper-catalyzed coupling. The "Ullmann-type" Reactions include
copper-catalyzed Nucleophilic Aromatic Substitution between various
nucleophiles (e.g. substituted phenoxides) with aryl halides. The most
common of these is the Ullmann Ether Synthesis.
Mechanism of the Ullmann Reaction
Biaryls are available through coupling of the aryl halide with an excess of
copper at elevated temperatures (200 °C). The active species is a
copper(I)-compound which undergoes oxidative addition with the second equivalent
of halide, followed by reductive elimination and the formation of the aryl-aryl
The organocopper intermediate can be generated at a more moderate 70 °C using
a novel thiophenecarboxylate reagent. The reaction otherwise follows the same
reaction path as above.
Another possibility is the use of Cu(I) for the oxidative coupling of
aryllithium compounds at low temperatures. This method can also be used to
generate asymmetric biaryls, after addition of the appropriate halide.
Ullmann-type reactions proceed through a catalytic cycle, and in one
mechanism the copper is postulated to undergo oxidation to Cu(III). As some
Cu(III) salts have been prepared, the suggestion for the
mechanism is intriguing (see also Chan-Lam Coupling):
Immobilization of Copper(II) in Organic-Inorganic Hybrid Materials: A Highly
Efficient and Reusable Catalyst for the Classic Ullmann Reaction
Q. Wu, L. Wang, Synthesis, 2008,
An Improved Cu-Based Catalyst System for the Reactions of Alcohols with Aryl
R. A. Altman, A. Shafir, P. A. Lichtor, S. L. Buchwald, J. Org. Chem., 2008,
An Efficient Ullmann-Type C-O Bond Formation Catalyzed by an Air-Stable
J. Niu, H. Zhou, Z. Li, J. Xu, S. Hu, J. Org. Chem., 2008,
(2-Pyridyl)acetone-Promoted Cu-Catalyzed O-Arylation of Phenols with
Aryl Iodides, Bromides, and Chlorides
Q. Zhang, D. Wang, X. Wang, K. Ding, J. Org. Chem., 2009,
1,1,1-Tris(hydroxymethyl)ethane as a New, Efficient, and Versatile Tripod
Ligand for Copper-Catalyzed Cross-Coupling Reactions of Aryl Iodides with
Amides, Thiols, and Phenols
Y.-J. Chen, H.-H. Chen, Org. Lett., 2006,
N,N-Dimethyl Glycine-Promoted Ullmann Coupling Reaction of Phenols and
D. Ma, Q. Cai, Org. Lett., 2003, 5, 3799-3802.
A General and Mild Ullmann-Type Synthesis of Diaryl Ethers
H.-J. Cristau, P. P. Cellier, S. Hamada, J.-F. Spindler, M. Taillefer,
Org. Lett., 2004, 6, 913-916.
CuI/Oxalic Diamide Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and
W. Zhou, M. Fan, J. Yin, Y. Jiang, D. Ma, J. Am. Chem. Soc., 2015,
CuI/DMPAO-Catalyzed N-Arylation of Acyclic Secondary Amines
Y. Zhang, X. Yang, Q. Yao, D. Ma, Org. Lett., 2012,
A Facile and Practical Copper Powder-Catalyzed, Organic Solvent- and
Ligand-Free Ullmann Amination of Aryl Halides
J. Jiao, X.-R. Zhang, N.-H. Chang, J. Wang, J.-F. Wei, X.-Y. Shi, Z.-G. Chen, J. Org. Chem., 2011,
Copper-Catalyzed Coupling of Alkylamines and Aryl Iodides: An Efficient System
Even in an Air Atmosphere
F. Y. Kwong, A. Klapars, S. L. Buchwald, Org.
2002, 4, 581-584.
Regioselective Copper-Catalyzed Amination of Bromobenzoic Acids Using
Aliphatic and Aromatic Amines
C. Wolf, S. Liu, X. Mei, A. T. August, M. D. Casimir, J. Org. Chem., 2006, 71, 3270-3273.
Efficient Copper-Catalyzed Synthesis of 4-Aminoquinazoline and
X. Yang, H. Liu, R. Qiao, Y. Jiang, Y. Zhao, Synlett, 2010,
Synthesis of Pyrroles via Copper-Catalyzed Coupling of Amines with
Y. Pan, H. Lu, Y. Fang, X. Fang, L. Chen, J. Qian, J. Wang, C. Li, Synthesis, 2007,
General and Highly Efficient Synthesis of 2-Alkylideneazetidines and
β-Lactams via Copper-Catalyzed Intramolecular N-Vinylation
H. Lu, C. Li, Org. Lett., 2006,
Preference of 4-exo Ring Closure in Copper-Catalyzed Intramolecular Coupling
of Vinyl Bromides with Alcohols
Y. Fang, C. Li, J. Am. Chem. Soc., 2007,
A General Method for the Formation of Aryl-Sulfur Bonds Using Copper(I)
C. G. Bates, R. K. Gujadhur, D. Venkataraman, Org.
Lett., 2002, 4, 2803-2806.
Ligand-Free Copper-Catalyzed Arylation of Amidines
M. Cortes-Salva, C. Garvin, J. C. Antilla, J. Org. Chem., 2011,