Liebeskind-Srogl Coupling

Liebeskind–Srogl Coupling

The Liebeskind–Srogl coupling is a significant reaction in organic chemistry, named after its inventors, Jiri Srogl from the Academy of Sciences, Czech Republic, and Lanny S. Liebeskind from Emory University, Atlanta, Georgia, USA. This reaction is a type of cross-coupling reaction that forms a new carbon–carbon bond, primarily between thioesters or sulfide electrophiles and boronic acids or esters[1].

Mechanism and Conditions

The reaction mechanism involves a palladium(0) catalyst and is characterized by the use of copper(I) thiophene-2-carboxylate (CuTC) as a co-catalyst or promoter. The original transformation utilizes catalytic Pd(0) with tris(2-furyl)phosphine (TFP) as an additional ligand. The process is desulfitative, meaning it involves the removal of a sulfonyl group during the coupling[1][5].

Substrates and Scope

The Liebeskind–Srogl coupling is versatile, applicable to a wide range of organosulfur derivatives as electrophiles, including (hetero)aryl sulfides, thioamides, sulfanyl alkynes, and thiocyanates. The reaction partners on the nucleophilic side are typically boronic acids or esters, which can be either alkyl or aryl in nature[1].

Applications

Since its introduction, the Liebeskind–Srogl coupling has garnered attention for its synthetic utility, particularly in cases where traditional methods for carbon–carbon bond formation may not be suitable. It has been employed in the synthesis of complex molecules, demonstrating its value in modern organic synthesis[5]. The reaction's ability to form ketones under neutral conditions, without the need for bases, further highlights its synthetic versatility[7].

Significance

The Liebeskind–Srogl coupling represents a new paradigm in carbon–carbon bond formation, offering an alternative to traditional cross-coupling reactions. Its development has expanded the toolkit available to chemists for constructing complex organic molecules, showcasing the ongoing innovation in the field of cross-coupling chemistry[1][5].

In summary, the Liebeskind–Srogl coupling is a powerful and versatile reaction in organic synthesis, enabling the formation of carbon–carbon bonds through the coupling of thioesters and boronic acids under palladium catalysis and copper promotion. Its broad substrate scope and applicability in synthesizing complex molecules underscore its importance in the field.

Citations:

[1] https://en.wikipedia.org/wiki/Liebeskind%E2%80%93Srogl_coupling

[2] https://onlinelibrary.wiley.com/doi/10.1002/ajoc.201700651

[3] https://onlinelibrary.wiley.com/doi/abs/10.1002/ajoc.201700651

[4] https://www.sciencedirect.com/topics/chemistry/liebeskind-srogl-coupling

[5] https://pubmed.ncbi.nlm.nih.gov/19067446/

[6] https://academic-accelerator.com/encyclopedia/liebeskind-srogl-coupling

[7] https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0041-1738243.pdf

[8] https://pubs.acs.org/doi/10.1021/jacs.8b13534

[9] https://pubs.acs.org/doi/abs/10.1021/acs.orglett.3c03873

[10] https://www.researchgate.net/publication/322087406_Recent_Advances_in_Liebeskind-Srogl_Cross-Coupling_and_its_Synthetic_Applications

[11] https://onlinelibrary.wiley.com/doi/full/10.1002/anie.200802842

[12] http://www.lac.dicp.ac.cn/member/yzk/13_yzk_pub.pdf

[13] https://typeset.io/papers/the-liebeskind-srogl-c-c-cross-coupling-reaction-tm9ftvt0s7

[14] https://en.wikipedia.org/wiki/Cross-coupling_reaction