View source for Chemistry:Chan-Lam coupling

{{Reactionbox
|Name = Chan-Lam coupling
|Type = Coupling reaction
|NamedAfter = Dominic Chan <br/> Patrick Lam
|Section3 = {{Reactionbox Identifiers
|OrganicChemistryNamed = chan-lam-coupling
|RSC_ontology_id = 0000374
}}
}}
The '''Chan–Lam coupling''' reaction – also known as the '''Chan–Evans–Lam coupling''' is a [[Chemistry:Cross-coupling reaction|cross-coupling reaction]] between an aryl [[Chemistry:Boronic acid|boronic acid]] and an [[Chemistry:Alcohol|alcohol]] or an [[Chemistry:Amine|amine]] to form the corresponding secondary aryl amines or aryl ethers, respectively.<ref>{{cite book|chapter=Recent Advances in Chan–Lam Coupling Reaction: Copper-Promoted C–Heteroatom Bond Cross-Coupling Reactions with Boronic Acids and Derivatives|author=Jennifer X. Qiao, Patrick Y.S. Lam|title=Boronic Acids: Preparation and Applications in Organic Synthesis, Medicine and Materials|editor=Dennis G. Hall|year=2011|pages=315–361|publisher=Wiley-VCH|doi=10.1002/9783527639328.ch6|isbn=9783527639328}}</ref> The Chan–Lam coupling is catalyzed by [[Chemistry:Copper|copper]] complexes. It can be conducted in air at room temperature. The more popular Buchwald–Hartwig coupling relies on the use of [[Chemistry:Palladium|palladium]].

==History==
Chan, Evans, and Lam published their work nearly simultaneously.<ref>{{cite journal|title=New N- and O-Arylations with Phenylboronic acids and Cupric Acetate|authors=Chan, Dominic; Monaco, Kevin; Wang, R.; Winter, Michael|journal=Tetrahedron Lett.|volume=39|year=1998|issue=19|pages=2933–2936|doi=10.1016/s0040-4039(98)00503-6}}</ref><ref>{{cite journal|title=Synthesis of Diaryl Ethers through the Copper-Promoted Arylation of Phenols with Arylboronic Acids. An Expedient Synthesis of Thyroxine|authors=Evans, David; Katz, J.; West, T.|journal=Tetrahedron Lett. |volume=39|year=1998|issue=19|pages=2937–2942|doi=10.1016/s0040-4039(98)00502-4}}</ref><ref>{{cite journal|title=New Aryl/Heteroaryl C-N Bond Cross-coupling Reactions via Arylboronic Acid/Cupric Acetate Arylation|authors=Lam, Patrick; Clark, Charles; Saubern, Simon; Adams, Jessica; Winters, Michael; Chan, Dominic; Combs, Andrew|journal=Tetrahedron Lett.|volume=39|year=1998|pages=2941–2944|doi=10.1016/s0040-4039(98)00504-8}}</ref><ref>{{cite journal|title=Copper-promoted/catalyzed C-N and C-O Bond Cross-coupling with Vinylboronic Acid and Its Utilities|authors=Lam, Patrick; Bonne, Damien; Vincent, Guillaume; Clark, Charles|journal=Tetrahedron Lett. |volume=44|year=2003|pages=4927–4931|doi=10.1016/s0040-4039(03)01037-2}}</ref><ref>{{cite journal|title=Copper Promoted C-N and C-O Bond Cross-coupling with Phenyl and Pyridylboronates|authors=Chan, Dominic; Monaco, Kevin; Li, Renhua; Bonne, Damien; Clark, Charles; Lam, Patrick|journal= Tetrahedron Lett.|volume=44|year=2003|pages=3863–3865|doi=10.1016/s0040-4039(03)00739-1}}</ref> the mechanism however remained mysterious for many years.

==Mechanism==
Analysis of the mechanism is complicated by the lability of copper reagents and the multicomponent nature of the reaction.<ref name=JACS>
{{cite journal|authors=Vantourout, J. C.; Miras, H. N.; Isidro-Llobet, A.; Sproules, S.; Watson, A. J. B.|title=Spectroscopic Studies of the Chan–Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity|journal=Journal of the American Chemical Society|year=2017|volume=139|issue=13|pages=4769–4779|doi=10.1021/jacs.6b12800|pmid=28266843|url=http://eprints.gla.ac.uk/139910/1/139910.pdf}}</ref> The reaction proceeds via the formation of copper-aryl complexes. A copper(III)-aryl-alkoxide or copper(III)-aryl-amide intermediate undergoes [[Chemistry:Reductive elimination|Reductive elimination]] to give the aryl ether or aryl amine, respectively:
:Ar-Cu(III)-NHR-L<sub>2</sub> → Ar-NHR + Cu(I)L<sub>2</sub>
:Ar-Cu(III)-OR-L<sub>2</sub> → Ar-OR + Cu(I)L<sub>2</sub>

==Example==
An example of the Chan–Lam coupling to synthesize biologically active compounds is shown below:
:[[File:Chanlamreactionexamplebellstein.pdf|center|750px|Reaction example of Chan–Lam coupling]]

Compound 1, a pyrrole, is coupled with aryl boronic ester, 2, to afford product 3, which is then carried forward to the target 4. The nitrile group of 2 does not poison the catalyst. [[Chemistry:Pyridine|Pyridine]] 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==
*{{cite journal|author1=Kodepelly Sanjeeva Rao|author2=Tian-Shung Wu|journal=Tetrahedron|title=Chan-Lam coupling reactions: synthesis of heterocycles|doi=10.1016/j.tet.2012.06.015|volume=68| year=2012|issue=38|pages=7735–7754}}

==References==
{{reflist}}
* https://www.princeton.edu/chemistry/macmillan/group-meetings/JLA_CopperMechanisticStudies.pdf

[[Category:Carbon-carbon bond forming reactions]]
[[Category:Name reactions]]

{{Sourceattribution|Chan-Lam coupling|1}}