Chan-Lam Coupling

This reaction allows aryl carbon-heteroatom bond formation via an oxidative coupling of boronic acids, stannanes or siloxanes with N-H or O-H containing compounds in air. Substrates include phenols, amines, anilines, amides, imides, ureas, carbamates, and sulfonamides. The reaction is induced by a stoichiometric amount of copper(II) or a catalytic amount of copper catalyst which is reoxidized by atmospheric oxygen or another primary oxidant.

The Chan-Lam Coupling may be conducted at room temperature in air, which gives it a certain advantage over the Buchwald-Hartwig Cross Coupling.

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Mechanism of the Chan-Lam Coupling

The reaction with a stoichiometric amount of copper(II) is also facilitated by oxygen, because reductive elimination from a copper(III) species is faster.

Recent Literature

Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity
J. C. Vantourout, H. N. Miras, A. Isidro-Llobet, S. Sproules, A. J. B. Watson, J. Am. Chem. Soc., 2017, 139, 4769-4779.

Ligand- and Base-Free Copper(II)-Catalyzed C-N Bond Formation: Cross-Coupling Reactions of Organoboron Compounds with Aliphatic Amines and Anilines
T. D. Quach, R. A. Batey, Org. Lett., 2003, 5, 4397-4400.

Copper(II) acetate catalyzes a coupling of arylboronic acids and amines in the presence of 2,6-lutidine as base, and myristic acid as an additive. Functionalized aniline substrates provided diarylamine coupling products in good yield, whereas alkylamines gave N-alkyl anilines in moderate yield.
J. C. Antilla, S. L. Buchwald, Org. Lett., 2001, 3, 2077-2079.

Copper(II)-Catalyzed Ether Synthesis from Aliphatic Alcohols and Potassium Organotrifluoroborate Salts
T. D. Quach, R. A. Batey, Org. Lett., 2003, 5, 1381-1384.

A Cu-catalyzed nondecarboxylative methylation of carboxylic acids with methylboronic acid proceeds in air as sole oxidant and offers a strategy for replacing toxic, electrophilic alkylating reagents. An isotope-labeling study supports an oxidative cross-coupling mechanism, in analogy to that proposed for Chan-Lam arylation.
C. E. Jacobson, N. Martinez-Muñoz, D. J. Gorin, J. Org. Chem., 2015, 80, 7305-7310.

Copper-Catalyzed N- and O-Alkylation of Amines and Phenols using Alkylborane Reagents
S. Sueki, Y. Kuninobu, Org. Lett., 2013, 15, 1544-1547.

Chan-Evans-Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the Aryl Amine Problem
J. C. Vantourout, R. P. Law, A. Isidro-Llobet, S. J. Atkinson, A. J. B. Watson, J. Org. Chem., 2016, 81, 3942-3950.

Selective Formation of Secondary Amides via the Copper-Catalyzed Cross-Coupling of Alkylboronic Acids with Primary Amides
S. A. Rossi, K. W. Shimkin, Q. Xu, L. M. Mori-Quiroz, D. A. Watson, Org. Lett., 2013, 15, 2314-2317.

An Efficient Base-Free N-Arylation of Imidazoles and Amines with Arylboronic Acids Using Copper-Exchanged Fluorapatite
M. L. Kantam, G. T. Venkanna, C. Sridhar, B. Sreedhar, B. M. Choudary, J. Org. Chem., 2006, 71, 9522-9524.

Nickel-Mediated N-Arylation with Arylboronic Acids: An Avenue to Chan-Lam Coupling
D. S. Raghuvanshi, A. K. Gupta, K. N. Singh, Org. Lett., 2012, 14, 4326-4329.

Chan-Lam Amination of Secondary and Tertiary Benzylic Boronic Esters
J. D. Grayson, F. M. Dennis, C. C. Robertson, B. M. Partridge, J. Org. Chem., 2021, 86, 9883-9897.

Synthesis of N-Aryl Amides by Ligand-Free Copper-Catalyzed ipso-Amidation of Arylboronic Acids with Nitriles
Y. Qiao, G. Li, S. Liu, Y. Yangkai, J. Tu, F. Xu, Synthesis, 2017, 49, 1834-1838.

A Synthetic Approach to N-Aryl Carbamates via Copper-Catalyzed Chan-Lam Coupling at Room Temperature
S.-Y. Moon, U. Bin Kim, D.-B. Sung, W.-S. Kim, J. Org. Chem., 2015, 80, 1856-1865.

Microwave-assisted conditions enabled a simple, rapid, one-pot synthesis of arylaminomethyl acetylenes in very good yields using arylboronic acids, aqueous ammonia, propargyl halides, copper(I) oxide and water as the solvent within ten minutes.
Y. Jiang, S. Huang, Synlett, 2014, 25, 407-410.

Synthesis of Diaryl Ethers through the Copper-Promoted Arylation of Phenols with Arylboronic Acids. An Expedient Synthesis of Thyroxine
D. A. Evans, J. L. Katz, T. R. West, Tetrahedron Letters, 1998, 39, 2937-2940.

Cu(OTf)₂-Mediated Chan-Lam Reaction of Carboxylic Acids to Access Phenolic Esters
L. Zhang, G. Zhang, M. Zhang, J. Cheng, J. Org. Chem., 2010, 75, 7472-7474.

Copper-Catalyzed Formamidation of Arylboronic Acids: Direct Access to Formanilides
V. P. Srivastava, D. K. Yadav, A. K. Yadav, G. Watal, L. D. S. Yadav, Synlett, 2013, 24, 1423-1427.

Copper-Catalyzed N-Arylation of Sulfonamides with Boronic Acids in Water under Ligand-Free and Aerobic Conditions
M. Nasrollahzadeh, A. Ehsani, M. Maham, Synlett, 2014, 25, 505-508.

Copper-Catalyzed Chan-Lam Coupling between Sulfonyl Azides and Boronic Acids at Room Temperature
S.-Y. Moon, J. Nam, K. Rathwell, W.-S. Kim, Org. Lett., 2014, 16, 338-339.

Copper-Catalyzed Nondecarboxylative Cross Coupling of Alkenyltrifluoroborate Salts with Carboxylic Acids or Carboxylates: Synthesis of Enol Esters
F. Huang, T. D. Quach, R. A. Batey, Org. Lett., 2013, 15, 3058-3061.

Copper-Promoted Coupling of Vinyl Boronates and Alcohols: A Mild Synthesis of Allyl Vinyl Ethers
R. E. Shade, A. M. Hyde, J.-C. Olsen, C. A. Merlic, J. Am. Chem. Soc., 2010, 132, 1202-1203.

Copper-Catalyzed Oxidative Acetalization of Boronic Esters: An Umpolung Strategy for Cyclic Acetal Synthesis
E. M. Miller, M. A. Walczak, J. Org. Chem., 2020, 85, 8230-8239.

New N- and O-arylations with phenylboronic acids and cupric acetate
D. M. T. Chan, K. L. Monaco, R.-P. Wang, M. P. Winteres, Tetrahedron Lett., 1998, 39, 2933-2936.

Selective Monomethylation of Anilines by Cu(OAc)₂-Promoted Cross-Coupling with MeB(OH)₂
I. González, J. Mosquera, C. Guerrero, R. Rodríguez, Jacobo Cruces, Org. Lett., 2009, 11, 1677-1680.

Selective Copper-Promoted Cross-Coupling of Aromatic Amines with Alkyl Boronic Acids
M. Larrosa, C. Guerrero, R. Rodríguez, J. Cruces, Synlett, 2010, 2101-2105.

Copper(II)-Catalyzed Conversion of Aryl/Heteroaryl Boronic Acids, Boronates, and Trifluoroborates into the Corresponding Azides: Substrate Scope and Limitations
K. D. Grimes, A. Gupte, C. C. Aldrich, Synthesis, 2010, 1441-1448.

Chan-Lam-Type S-Arylation of Thiols with Boronic Acids at Room Temperature
H.-J. Xu, Y.-Q. Zhao, T. Feng, Y.-S. Feng, J. Org. Chem., 2012, 77, 2649-2658.

An Efficient Copper-Catalyzed One-Pot Synthesis of Diaryl Thioethers by Coupling of Arylboronic Acids with Potassium Ethyl Xanthogenate under Mild Conditions
L. Wang, W.-Y. Zhou, S.-C. Chen, M.-Y. He, Q. Chen, Synlett, 2011, 3041-3045.

Chan-Lam-Type C-S Coupling Reaction by Sodium Aryl Sulfinates and Organoboron Compounds
L. Y. Lam, C. Ma, Org. Lett., 2021, 23, 6164-6168.

Copper-Mediated Cross-Coupling of Aryl Boronic Acids and Alkyl Thiols
P. S. Herradura, K. A. Pendola, R. K. Guy, Org. Lett., 2000, 2, 2019-2022.

Chan-Lam-Type C-S Coupling Reaction by Sodium Aryl Sulfinates and Organoboron Compounds
L. Y. Lam, C. Ma, Org. Lett., 2021, 23, 6164-6168.

A cross-coupling reaction of arylboronic acids with KSCN salt to yield aryl thiocyanates is catalyzed by copper acetate in the presence of 4-methylpyridine serving both as ligand and base under 0.2 MPa of molecular oxygen. Various arylboronic acids were suitable under the reaction conditions.
N. Sun, H. Zhang, W. Mo, B. Hu, Z. Shen, X. Hu, Synlett, 2013, 24, 1443-1447.

Copper-Mediated Coupling of Boronic Acids, Amines, and Carbon Disulfide: An Approach to Organic Dithiocarbamates
C. Qi, T. Guo, W. Xiong, Synlett, 2016, 27, 2626-2630.

Copper-Catalyzed N-Arylation of Sulfoximines with Arylboronic Acids under Mild Conditions
S. Gupta, S. Baranwal, N. Muniyappan, S. Sabiah, J. Kandasamy, Synthesis, 2019, 51, 2171-2182.

Biomolecule-Compatible Dehydrogenative Chan-Lam Coupling of Free Sulfilimines
T. Meng, L. A. Wells, T. Wang, J. Wang, S. Zhang, J. Wang, M. C. Kozlowski, T. Jia, J. Am. Chem. Soc., 2022, 144, 12476-12487.

Sulfur-Arylation of Sulfenamides via Chan-Lam Coupling with Boronic Acids: Access to High Oxidation State Sulfur Pharmacophores
N. S. Greenwood, J. A. Ellman, Org. Lett., 2023, 25, 2830-2834.

Copper-Catalyzed C-P Bond Construction via Direct Coupling of Phenylboronic Acids with H-Phosphonate Diesters
R. Zhuang, J. Xu, Z. Cai, G. Tang, M. Fang, Y. Zhao, Org. Lett., 2011, 13, 2110-2113.

Copper(I) Oxide Catalyzed N-Arylation of Azoles and Amines with Arylboronic Acid at Room Temperature under Base-Free Conditions
B. Sreedhar, G. T. Venkanna, K. B. S. Kumar, V. Balasubrahmanyam, Synthesis, 2008, 795-799.

An Efficient Diamine·Copper Complex-Catalyzed Coupling of Arylboronic Acids with Imidazoles
J. P. Collman, M. Zhong, Org. Lett., 2000, 2, 1233-1236.

New aryl/heteroaryl C-N bond cross-coupling reactions via arylboronic acid/cupric acetate arylation
P. Y. S. Lam, C. G. Clark, S. Saubern, J. Adams, M. P. Winters, D. M. T. Chan, A. Combs, Tetrahedron Lett., 1998, 39, 2941-2944.

Comparison of Copper(II) Acetate Promoted N-Arylation of 5,5-Dimethyl Hydantoin and Other Imides with Triarylbismuthanes and Aryl Boronic Acids
H. M. Hügel, C. J. Rix, K. Fleck, Synlett, 2006, 2290-2292.

CuF₂/MeOH-Catalyzed N³-Selective Chan-Lam Coupling of Hydantoins: Method and Mechanistic Insight
T. Roy, K. Mondal, A. Sengupta, P. Das, J. Org. Chem., 2023, 88, 6058-6070.

One-Pot Approach to 1,2-Disubstituted Indoles via Cu(II)-Catalyzed Coupling/Cyclization under Aerobic Conditions and Its Application for the Synthesis of Polycyclic Indoles
J. Gao, Y. Shao, J. Zhu, H. Mao, X. Wang, X. Lv, J. Org. Chem., 2014, 79, 9000-9008.

One-Pot, Multistep Reactions for the Modular Synthesis of N,N'-Diarylindazol-3-ones
S. Liu, L. Xu, Y. Wei, J. Org. Chem., 2019, 84, 1596-1604.

Concise Synthesis of N-Aryl Tetrahydroquinolines via a One-Pot Sequential Reduction of Quinoline/Chan-Evans-Lam Coupling Reaction
D. Bhattacharyya, S. K. Senapati, A. Das, Synlett, 2023, 34, 651-656.

Copper-Catalyzed Reactions of Alkenyl Boronic Esters via Chan-Evans-Lam Coupling/Annulation Cascades: Substrate Selective Synthesis of Dihydroquinazolin-4-ones and Polysubstituted Quinolines
Y. Li, Z. Cao, Z. Wang, L. Xu, Y. Wei, Org. Lett., 2022, 24, 6554-6559.