Chan–Lam coupling

The Chan–Lam coupling reaction – also known as the Chan–Evans–Lam coupling is a

Dominic Chan, David Evans, and Patrick Lam published their work nearly simultaneously.^{[2][3][4][5][6]} The mechanism however remained uncertain for many years. Later developments by others extended the scope to include using carboxylic acids, giving aryl-ester products.^[7]

Mechanism

Analysis of the mechanism is complicated by the lability of copper reagents and the multicomponent nature of the reaction.^[8] The reaction proceeds via the formation of copper-aryl complexes. A copper(III)-aryl-alkoxide or copper(III)-aryl-amide intermediate undergoes Reductive elimination to give the aryl ether or aryl amine, respectively:

Ar-Cu(III)-NHR-L₂ → Ar-NHR + Cu(I)L₂

Ar-Cu(III)-OR-L₂ → Ar-OR + Cu(I)L₂

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

• Kodepelly Sanjeeva Rao; Tian-Shung Wu (2012). "Chan-Lam coupling reactions: synthesis of heterocycles". Tetrahedron. 68 (38): 7735–7754.
  doi:10.1016/j.tet.2012.06.015
  .