Liebeskind-Srogl coupling

The Liebeskind-Srogl coupling is a palladium catalyzed coupling between a thioes-ter and a boronic acid. It was first reported by Liebeskind and Srogl (2000). In this reaction, Pd2 (dba)3 was used as a palladium precursor and copper (I) thiophene-2-carboxylate (CuTC) as a mediator. 

Nutlin-like structures can be achieved by performing this coupling between aryl-boronic acids and imidazolidine-2-thiones, prepared by a novel MCR. Microwave-assisted Liebeskind-Srogl couplings gave desired Nutlin derivatives (the so-called Nutloids) in fair yields. 

Bon et al. (2008) optimized this procedure of Liebeskind-Srogl couplings of im-idazolidine-2-thiones with arylboronic acids, affording Nutloids in 41-65% yields. 

Scheme 6.SS Palladium(0)-catalyzed, copper(l)-mediated Liebeskind-Srogl-type couplings.

Other references related to the Liebeskind-Srogl cross-coupling are cited in the... 

Hintermann and his group prepared Soai aldehydes, 2-(alkynyl)-l,3-pyrimidine-5-carbaldehydes, in the absence of base, via a Liebeskind—Srogl cross-coupling reaction of terminal alkynes with 2-mercapto-l,3-pyrimi-dine-5-carbaldehyde (55) (Scheme 37) (140L1282). Optimal conditions for this synthesis were determined to be stirring of 1 equivalent of mer-captoaldehyde 55 with 1.5-2.0 equivalents of the terminal alkyne in a microwave reactor in the presence of 2.0 equivalents of copper(I)... 

Arylthiocyclobutenediones may be considered as vinylogous thiol esters. As such, they were expected to participate in the Liebeskind-Srogl cross-coupling. Thus, (2) was exposed to a variety of horonic acids under the Lieheskind conditions to give the corresponding symmetrical cyclohutenediones (eq 16). ... 

The first example of a Liebeskind-Srogl cross-coupling reaction in water was reported (13JHC1368). Specifically, 2-(methylthio)pyridine and 2-(methylthio)benzothiazole were treated with a series of arylboronic acids in the presence of Pd(0) catalyst and thiophene-2-carboxylate. 

Prokopcova et al. (2005) performed thioether-boronic acid cross-coupling (Liebeskind-Srogl reaction) using microwave heating involving C-C cross-coupling... 

A series of new a-nucleophiles (738) has been synthesised, and their ability to efficiently and selectively cleave the P-S bond of organo-phosphorus nerve agents (737), has been evaluated. This reaction led to the new non-toxic phosphonic acid (739) and aminothiol (740) (Scheme 187). ° A series of novel pyrimidine based, acyclic nucleoside phosphonates (742), has been prepared, using the Liebeskind-Srogl cross-coupling protocol involving highly functionalised 2-(methylsulfanyl)pyrimidines (741) and various arylboronic acids (Scheme 188). " ... 

Savarin, C. Srogl, J. Liebeskind, L. S. Thiol ester-boronic acid cross-coupling. Catalysis using alkylative activation of the Pd thiolate intermediate. Org. Lett. 2000, 2, 3229-3231. 

In 2000, Liebeskind and Srogl reported a Pd-catalyzed boronic acid-thioether crosscoupling protocol which was mediated by copper(I)-carboxylate [68]. Recognizing their increased accessibility, this protocol was successfully applied to the Stille-type coupling reactions of organostannanes with heteroaromatic thioethers [69]. Specifically, the Pd-catalyzed reaction of 122 and stannane 123 was promoted by copper(I)-3-methylsalicy-late to provide 124 in excellent yield. 

Liebeskind and Srogl developed Pd-catalyzed cross-coupling of simple thiol esters with boronic acids to give ketones in the presence of Cu(I) thiophene-2-carboxylate (CuTC) under nonbasic conditions (Eq. 25) [50]. 

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