What Is Chan-Lam Coupling Reaction?
The Chan-Lam coupling reaction stands as a versatile and efficient method for forging C-heteroatom bonds (such as C-N and C-O bonds) in organic synthesis. Chan-Lam coupling reactions refer to the reaction of aroma-linked carbon-miscellaneous atomic bonds with compounds containing N-H or O-H bonds. In this reaction, the catalyst is a two -valent copper salt measured by chemical measurement, or a copper catalyst that can catalyze the oxygen oxidation in the air.
Fig 1. Chan-Lam coupling reaction and its mechanism. [1]
Mechanism of Chan-Lam Coupling Reaction
Phenol is deprotonated under the action of pyridine and reacts with copper acetate to form conjugate A. This cooperative with a metal exchange reaction with the boric acid generates a partner B, and then restores the one -price copper to get the coupling product. In addition, B can generate three -valent copper salt cooperative C with oxygen, and C can also be restored to eliminate the product.
Advantages of Chan-Lam Coupling Reaction
- Mild Reaction Conditions: The reaction can be conducted at room temperature or with mild heating, making it suitable for substrates sensitive to harsh conditions.
- Air and Moisture Tolerance: Unlike many palladium-catalyzed cross-coupling reactions, the Chan-Lam coupling tolerates air and moisture, simplifying reaction setup and handling.
- Broad Substrate Scope: The substrates include phenols, amines, anilines, azoles, amides, ureas, carbamates, and sulfonamides.
- Copper Availability: Copper is a readily available and inexpensive transition metal compared to precious metals like palladium.
Application Examples of Chan-Lam Coupling Reaction
Chan-Lam coupling reaction for C-N bonds formation
The application of Chan-Lam coupling reaction in the field of C-N bond construction includes the construction of C-N bonds between primary amines and arylboronic acids, the construction of C-N bonds of nitrogen-containing heterocyclic compounds, the construction of C-N bonds of azides and sulfonamide compounds, etc. In addition, Zhu and co-workers also reported a one-pot synthesis of 2-arylbenzimidazoles and their derivatives via Cu-catalyzed Chan-Lam coupling of arylboronic acids with amidines. Mono-N-arylation and subsequent direct C-H bond functionalization form C-N bonds in the same catalytic system. The protocol involves a domino strategy and does not require the isolation of intermediates. [2]
Chan-Lam coupling reaction for C-O bonds formation
Anderson and colleagues described a novel approach for synthesizing α-oxygenated ketones and substituted catechols through the rearrangement of Nenoxy- and N-aryloxyphthalimides, prepared by the Chan-Lam coupling reaction. N-hydroxyphthalimide efficiently reacted with alkenylboronic acids or arylboronic acids to produce the desired compounds under mild conditions, using copper(II) acetate as the catalyst, bipyridine as the ligand, sodium sulfate as the base, ambient air, and dichloroethane as the solvent at room temperature. [3]
Chan-Lam coupling reaction for C-S bonds formation
Krouzelka et al. devised a simple method for synthesizing N-acetyl-S-arylcysteines from N,N'-diacetylcystine dimethyl esters and arylboronic acids using a copper salt catalyst. This approach utilized readily available disulfides as starting materials and inexpensive copper acetate as the mediator. [4]
Fig 2. Synthetic examples via Chan-Lam coupling reaction.
Related Products
References
- Chen, Jin‐Quan, et al. Advanced Synthesis & Catalysis, 2020, 362(16), 3311-3331.
- Li, Jihui, et al. Organic letters, 2012, 14(23), 5980-5983.
- Kroc, Michelle A., et al. Tetrahedron, 2017, 73(29), 4125-4137.
- Krouželka, Jan, et al. EurJOC, 2009, 36, 6336-6340.
