The Chan–Lam coupling reaction, also known as the Chan–Evans–Lam coupling, is a
cross-coupling reaction
In organic chemistry, a cross-coupling reaction is a reaction where two different fragments are joined. Cross-couplings are a subset of the more general coupling reactions. Often cross-coupling reactions require metal catalysts. One important re ...
between an aryl
boronic acid
A boronic acid is an organic compound related to boric acid () in which one of the three hydroxyl groups () is replaced by an alkyl or aryl group (represented by R in the general formula ). As a compound containing a carbon–boron bond, memb ...
and an
alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
or an
amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
to form the corresponding secondary aryl amines or
aryl ether
In organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R′ r ...
s, respectively. The Chan–Lam coupling is catalyzed by
copper
Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...
complexes. It can be conducted open to air at room temperature. The more popular
Buchwald–Hartwig coupling relies on the use of
palladium
Palladium is a chemical element; it has symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1802 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas (formally 2 Pallas), ...
.
History
Dominic Chan,
David Evans, and Patrick Lam published their work nearly simultaneously. The mechanism however remained uncertain for many years. Later developments by others extended the scope to include using
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
s, giving aryl-ester products.
Mechanism
Analysis of the mechanism is complicated by the lability of copper reagents and the multicomponent nature of the reaction.
[
] The reaction proceeds via the formation of copper-aryl complexes. A copper(III)-aryl-alkoxide or copper(III)-aryl-amide intermediate undergoes
Reductive elimination
Reductive elimination is an elementary step in organometallic chemistry in which the oxidation state of the metal center decreases while forming a new covalent bond between two ligands. It is the microscopic reverse of oxidative addition, and is ...
to give the aryl ether or aryl amine, respectively:
:Ar-Cu(III)-NHR-L
2 → Ar-NHR + Cu(I)L
2
:Ar-Cu(III)-OR-L
2 → Ar-OR + Cu(I)L
2
Example
An example of the Chan–Lam coupling to synthesize biologically active compounds is shown below:
:
Compound 1, a pyrrole, is coupled with aryl boronic acid, 2, to afford product 3, which is then carried forward to the target 4. The
nitrile group of 2 does not poison the catalyst.
Pyridine
Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...
is the ligand used for the reaction. Although the reaction requires three days, it was carried out at room temperature in ambient air and resulted in a 93% yield.
Further reading
*
References
{{DEFAULTSORT:Chan-Lam coupling
Carbon-carbon bond forming reactions
Name reactions