Aryl derivatives Sonogashira coupling reactions

Scheme 7.18. Examples of the Sonogashira coupling reaction. In reaction (a), an aryl halide (X = Br, I) is coupled to the terminus of the (p-methylphenyl)ethyne. In reaction (b)> coupling is to a haloethene, prodncmg a substituted vrnylacetylene derivative. In both cases, catalytic (not stoichiometric) qnantities of palladium and copper catalysts are used.

Miura et al. reported the first palladium-free Sonogashira coupling reaction of aryl iodides or vinyl iodides with terminal allqmes in the presence of a copper iodide/triphenylphosphine/potassium carbonate catalyst system (Scheme 15.14). o-Iodo-acetanilide derivatives react with l-allg nes smoothly even at room temperature in the presence of a copper iodide/AT-methylpyrrolidine-2-carboxamide catalyst system (Scheme Various... 

Heck and Suzuki coupling reactions with bromo-oxepine 65 afforded 2-deoxy-2-alkyl/aryl septanosides. For example, Heck reaction of 65 with acrylates and styrene led to a high yield of coupled products groups as 86, whereas the use of a-methyl styrene furnished 87, in which the exo-cyc ic double bond isomerized to a terminal double bond. Suzuki coupling reaction with substituted phenylboronic acid led to 2-deoxy-2-C-aryl septanoside derivatives 88 in good yields. On the contrary, Sonogashira coupling reaction of 65 with acetylenes furnished 2-deoxy-2-C-alkenyl septanoside 89 (Scheme 13.24). 

Copper(I) derivatives of metal diynyl complexes have proven to be useful synthetic intermediates in Cadiot-Chodkiewicz coupling reactions,290 292 and similar species are implicated in coupling of metal diynyls with aryl halides under Pd/Cu catalyzed (Sonogashira) conditions241,242 and in the Cul-catalyzed coupling reactions of metal diynyl species with other metal halides.293... 

Under certain conditions, alkynes can be coupled to aryl halides.280 When aryl halides react with copper acetylides to give 1-aryl alkynes such as 431, the reaction is known as Stephens-Castro coupling.28l Both aliphatic and aromatic substituents can be attached to the alkyne unit, and a variety of aryl iodides has been used. A palladium-catalyzed variation is also known in which an aryl halide reacts with a terminal alkyne to give derivatives such as 434. In this variation, called the Sonogashira coupling,2 2 jhe reaction is catalyzed by... 

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]. 

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