Sonogashira coupling aryl-alkynyl

Water as a green solvent has been successfully applied as a reaction medium for palladium-catalyzed carbonylative Sonogashira reactions (Scheme 5.11) [36]. Instead of using alkynes, activated acetylenes stibanes can also be applied as coupling partners in carbonylations. An example is the palladium-catalyzed carbonylative Sonogashira coupling of alkynyl stibanes with aryl iodides that was published by Kakusawa and Kurita in 2006 [37], The reaction was carried out under 1 bar of CO in DMAc using 5 mol% of Pd(OAc)2 and 20 mol% of PPhs. 

Very recently Ryu and coworkers disclosed radical carbonylation/Sonogashira coupling sequences (Fig. 44) [218]. The reaction is applicable to primary, secondary, and tertiary alkyl iodides 177, and terminal aryl or alkyl alkynes 185. Alkynyl... 

Iodobenzyl 2-butynyl ethers undergo a Pd-mediated cyclisation with terminal alkynes to give lf/-[2]benzopyrans. The absence of a Cu(I) co-catalyst allows an intramolecular 6-exo-dig cyclisation to compete successfully with an intermolecular Sonogashira aryl-alkynyl coupling <02T9007>. 

Aryl-Alkynyl Coupling (Sonogashira Reaction) Reaction Conditions and Catalysts... 

In the former case, the reachon of [PdAr(I)Ln], where L is electron-rich PEt3, was examined (Scheme 6.31). Here, the reachon between the palladium complex, with R = Me, and lequiv. of [Cu(CCPh)(PPh3)]4 led to 74% of the Sonogashira product along with unreacted starting material. When the palladium copper ratio was decreased to 1 2, full conversion to the coupling product was observed. The intermediate of this reachon, an aryl(alkynyl)palladium complex, was formed in 65% as its trans-isomer, when the reaction temperature was lowered to -30 °C. The... 

In 1991 Ortar and colleagues published a general procedure for tbe carbonylative Sonogashira couplings of vinyl triflates with terminal acetylenes [28]. Various alkynyl ketones were produced in moderate to good yields (Scheme 5.5). However, this methodology failed in the case of activated alkynes or aryl triflates. 

With the development of Buchwald-Hartwig amination reactions, the amine component of these indoles can also be introduced into these precursors via palladium catalysis [8]. As shown by Ackermann, this can be coupled with aryl halide alkynylation and cyclization to provide a one-pot, three-component synthesis of substituted indoles (Scheme 6.6) [9]. In this case, simple ortho-dihaloarene derivatives S were employed as starting materials, with Sonogashira coupling occurring at the more activated aryl-iodide bond, followed by selective coupling of various alkyl or arylamines. Alternatively, Zhao has recently demonstrated that amination can be performed on both bromoalkyne 6, followed by the aryl-bromide bond, to provide a route to 2-amidoindoles (Scheme 6.7) [10]. 

The last Pd(0) catalyzed cross-coupling reaction covered in this chapter is the Sonogashira coupling. It involves transmetallation of an alkynyl-Cufl) species to Pd followed by coupling to an aryl or vinyl iodide or triflate. The Cu(I) alkynyl complex is created in situ by the reaction of a terminal alkyne with Cul in the presence of trieth-ylamine. The reaction is most commonly used to create diaryl alkynyl products. 

Colacot TJ, Li H, Pu X (2013) Heck alkynylation (copper-free sonogashira coupling) of aryl and heteroaryl chlorides, using Pd complexes of t-Bu2(p-NMe2C6lLi)P understanding the structure-activity relationships and copper effects. J Org Chem 78 568-581... 

Cu-catalyzed alkynation of L Pd and cross-coupling with R -X, has developed into a widely used method for forming new C-C bonds between alkynyl and aryl or vinyl groups. This transformation is now called Sonogashira cross-coupling. Equation 12.72 shows a typical example of the Sonogashira reaction.146... 

Alkynyltrimethylsilanes act as effective alkynyl donors in the presence of a fluoride ion source [15]. Recent studies on the Sonogashira-type reaction of alkynylsilanes have revealed that the use of a Cu(I) [554] or Ag(I) [555] salt leads to highly efficient coupling with vinyl and aryl triflates (Scheme 10.213). 

Sonogashira reaction [4,5], A comprehensive review on Pd-catalyzed alkynylation was published recently by Negishi and Anastasia [6], Facile Pd(0)-CuI-catalyzed coupling of aryl and alkenyl halides with 1-alkynes is used extensively for the preparation of arylalkynes or enynes. 

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