Buchwald-Hartwig Cross Coupling Reaction

Palladium-catalyzed synthesis of aryl amines. Starting materials are aryl halides or pseudohalides (for example triflates) and primary or secondary amines.

The synthesis of aryl ethers and especially diaryl ethers has recently received much attention as an alternative to the Ullmann Ether Synthesis.

Newer catalysts and methods offer a broad spectrum of interesting conversions.

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Mechanism of the Buchwald-Hartwig Coupling

Recent Literature

[(CyPF-tBu)PdCl₂]: An Air-Stable, One-Component, Highly Efficient Catalyst for Amination of Heteroaryl and Aryl Halides
Q. Sheng, J. F. Hartwig, Org. Lett., 2008, 10, 4109-4112.

A Multiligand Based Pd Catalyst for C-N Cross-Coupling Reactions
B. P. Fors, S. L. Buchwald, J. Am. Chem. Soc., 2010, 132, 15914-15917.

New Ammonia Equivalents for the Pd-Catalyzed Amination of Aryl Halides
X. Huang, S. L. Buchwald, Org. Lett., 2001, 3, 3417-3419.

Palladium-Catalyzed Synthesis of Arylamines from Aryl Halides and Lithium Bis(trimethylsilyl)amide as an Ammonia Equivalent
S. Lee, M. Jørgensen, J. F. Hartwig, Org. Lett., 2001, 3, 2729-2732.

Palladium-Catalyzed Coupling of Ammonia with Aryl Chlorides, Bromides, Iodides, and Sulfonates: A General Method for the Preparation of Primary Arylamines
G. D. Vo, J. F. Hartwig, J. Am. Chem. Soc., 2009, 131, 11049-11061.

Palladium-Catalyzed Amination of Aryl Chlorides and Bromides with Ammonium Salts
R. A. Green, J. F. Hartwig, Org. Lett., 2014, 16, 4388-4391.

Rational Ligand Design for the Arylation of Hindered Primary Amines Guided by Reaction Progress Kinetic Analysis
P. Ruiz-Castillo, D. G. Blackmond, S. L. Buchwald, J. Am. Chem. Soc., 2015, 137, 3085-3092.

General and Efficient Catalytic Amination of Aryl Chlorides Using a Palladium/Bulky Nucleophilic Carbene System
J. Huang, G. Grasa, S. P. Nolan, Org. Lett., 1999, 1, 1307-1309.

(IPr)Pd(acac)Cl: An Easily Synthesized, Efficient, and Versatile Precatalyst for C-N and C-C Bond Formation
N. Marion, E. C. Ecarnot, O. Navarro, D. Amoroso, A. Bell, S. P. Nolan, J. Org. Chem., 2006, 71, 3816-3821.

Synthesis of Bulky and Electron-Rich MOP-type Ligands and Their Applications in Palladium-Catalyzed C-N Bond Formation
X. Xie, T. Y. Zhang, Z. Zhang, J. Org. Chem., 2006, 71, 6522-6529.

Flexible Steric Bulky Bis(Imino)acenaphthene (BIAN)-Supported N-Heterocyclic Carbene Palladium Precatalysts: Catalytic Application in Buchwald-Hartwig Amination in Air
X.-B. Lan, Y. Li, Y.-F. Li, D.-S. Shen, Z. Ke, F.-S. Liu, J. Org. Chem., 2017, 82, 2914-2925.

Pd-PEPPSI-IPent^An Promoted Deactivated Amination of Aryl Chlorides with Amines under Aerobic Conditions
F.-D. Huang, C. Xu, D.-D. Lu, D.-S. Shen, T. Li, F.-S. Liu, J. Org. Chem., 2018, 83, 9144-9155.

Sterically Hindered Amination of Aryl Chlorides Catalyzed by a New Carbazolyl-Derived P,N-Ligand-Composed Palladium Complex
W. I. Lai, M. P. Leung, P. Y. Choy, F. Y. Kwong, Synthesis, 2019, 51, 2678-2686.

High Turnover Number and Rapid, Room-Temperature Amination of Chloroarenes Using Saturated Carbene Ligands
S. R. Stauffer, S. Lee, J. P. Stambuli, S. I. Hauck, J. F. Hartwig, Org. Lett., 2000, 2, 1423-1426.

Triazole-Based Monophosphine Ligands for Palladium-Catalyzed Cross-Coupling Reactions of Aryl Chlorides
Q. Dai, W. Gao, D. Liu, L. M. Kapes, X. Zhang, J. Org. Chem., 2006, 71, 3928-3934.

Bulky Alkylphosphines with Neopentyl Substituents as Ligands in the Amination of Aryl Bromides and Chlorides
L. L. Hill, L. R. Moore, R. Huang, R. Craciun, A. J. Vincent, D. A. Dixon, J. Chou, C. J. Woltermann, K. H. Shaughnessy, J. Org. Chem., 2006, 71, 4951-4955.

Water-Mediated Catalyst Preactivation: An Efficient Protocol for C-N Cross-Coupling Reactions
B. P. Fors, P. Krattiger, E. Strieter, S. L. Buchwald, Org. Lett., 2008, 10, 3505-3508.

Rational and Predictable Chemoselective Synthesis of Oligoamines via Buchwald-Hartwig Amination of (Hetero)Aryl Chlorides Employing Mor-DalPhos
B. J. Tardiff, R. McDonald, M. J. Ferguson, M. Stradiotto, J. Org. Chem., 2012, 77, 1056-1071.

Palladium-Catalyzed Synthesis of N,N-Dimethylanilines via Buchwald-Hartwig Amination of (Hetero)aryl Triflates
T. Taeufer, J. Pospech, J. Org. Chem., 2020, 85, 7097-7111.

Buchwald-Hartwig Amination of (Hetero)Aryl Tosylates Using a Well-Defined N-Heterocyclic Carbene/Palladium(II) Precatalyst
Y. Zhang, G. Lavigne, V. César, J. Org. Chem., 2015, 80, 7666-7673.

A Highly Active Catalyst for Pd-Catalyzed Amination Reactions: Cross-Coupling Reactions Using Aryl Mesylates and the Highly Selective Monoarylation of Primary Amines Using Aryl Chlorides
B. P. Fors, D. A. Watson, M. R. Biscoe, S. L. Buchwald, J. Am. Chem. Soc., 2008, 130, 13552-13554.

Palladium-Catalyzed Monoarylation of Aryl Amine with Aryl Tosylates
X. Xie, G. Ni, F. Ma, L. Ding, S. Xu, Z. Zhang, Synlett, 2011, 955-958.

Cross-Coupling and Dehalogenation Reactions Catalyzed by (N-Heterocyclic carbene)Pd(allyl)Cl Complexes
O. Navarro, H. Kaur, P. Mahjoor, S. P. Nolan, J. Org. Chem., 2004, 69, 3173-3180.

Expedited Palladium-Catalyzed Amination of Aryl Nonaflates through the Use of Microwave-Irradiation and Soluble Organic Amine Bases
R. E. Tundel, K. W. Anderson, S. L. Buchwald, J. Org. Chem., 2006, 71, 430-433.

Palladium- and Nickel-Catalyzed Aminations of Aryl Imidazolylsulfonates and Sulfamates
L. Ackermann, R. Sandmann, W. Song, Org. Lett., 2011, 13, 1784-1786.

An Air and Thermally Stable One-Component Catalyst for the Amination of Aryl Chlorides
D. Zim, S. L. Buchwald, Org. Lett., 2003, 5, 2413-2415.

(t-Bu)₂PNP(i-BuNCH₂CH₂)₃N: New Efficient Ligand for Palladium-Catalyzed C-N Couplings of Aryl and Heteroaryl Bromides and Chlorides and for Vinyl Bromides at Room Temperature
Ch. V. Reddy, J. V. Kingston, J. G. Verkade, J. Org. Chem., 2008, 73, 3047-3062.

Use of Polymer-Supported Dialkylphosphinobiphenyl Ligands for Palladium-Catalyzed Amination and Suzuki-Reaktions
C. A. Parrish, S. L. Buchwald, J. Org. Chem., 2001, 66, 3820-3827.

Pd/PTABS: Catalyst for Room Temperature Amination of Heteroarenes
S. S. M. Bandaru, S. Bhilare, N. Chrysochos, V. Gayakhe, I. Trentin, C. Schulzke, A. R. Kapdi, Org. Lett., 2018, 20, 473-476.

(t-Bu)₂PNP(i-BuNCH₂CH₂)₃N: New Efficient Ligand for Palladium-Catalyzed C-N Couplings of Aryl and Heteroaryl Bromides and Chlorides and for Vinyl Bromides at Room Temperature
Ch. V. Reddy, J. V. Kingston, J. G. Verkade, J. Org. Chem., 2008, 73, 3047-3062.

Amination Reactions of Aryl Halides with Nitrogen-Containing Reagents Mediated by Palladium/Imidazolium Salt Systems
G. A. Grasa, M. S. Viciu, J. Huang, S. P. Nolan, J. Org. Chem., 2001, 66, 7714-7722.

Rapidly Activating Pd-Precatalyst for Suzuki-Miyaura and Buchwald-Hartwig Couplings of Aryl Esters
A. H. Dardir, P. R. Melvin, R. M. Davis, N. Hazari, M. M. Beromi, J. Org. Chem., 2018, 83, 469-477.

The Role of Reversible Oxidative Addition in Selective Palladium(0)-Catalyzed Intramolecular Cross-Couplings of Polyhalogenated Substrates: Synthesis of Brominated Indoles
S. G. Newman, M. Lautens, J. Am. Chem. Soc., 2010, 132, 11416-11417.

Efficient Palladium-Catalyzed N-Arylation of Indoles
D. W. Old, M. C. Harris, S. L. Buchwald, Org. Lett., 2000, 2, 1403-1406.

Trivalent Organostibines: Sb,N Ligands in Double N-Arylation of Primary Amines toward Functionalized Carbazoles
L. Peng, Y. Zhao, J. Chen, H. Lu, Z. Tang, Y. Chen, S.-F. Yin, N. Kambe, R. Qiu, J. Org. Chem., 2024, 89, 183-190.

A new reactivity pattern for vinyl bromides: cine-substitution via palladium catalysed C-N coupling/Michael addition reactions
M. C. Willis, J. Chauhan, W. G. Whittinham, Org. Biomol. Chem., 2005, 3, 3094-3095.

Significantly Improved Method for the Pd-Catalyzed Coupling of Phenols with Aryl Halides: Understanding Ligand Effects
C. H. Burgos, T. E. Barder, X. Huang, S. L. Buchwald, Angew. Chem. Int. Ed., 2006, 45, 4321-4326.