Aryl halides alkynylation

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]. 

Alkenylboranes (R2C=CHBZ2 Z — various groups) couple in high yields with vinylic, alkynyl, aryl, benzylic, and allylic halides in the presence of tetra-kis(triphenylphosphine)palladium, Pd(PPh3)4, and a base to give R C CHR. 9-Alkyl-9-BBN compounds (p. 1013) also couple with vinylic and aryl halides " as well as with a-halo ketones, nitriles, and esters.Aryl halides couple with ArB(IR2 ) species with a palladium catalyst. ... 

Palladium And/Or Copper-Mediated Cross-Coupling Reactions Between 1-Alkynes And Vinyl, Aryl, 1-Alkynyl, 1,2-Propadienyl, Propargyl And Allylic Halides Or Related Compounds. A Review, Rossi. R. Carpita, A. Beilina, F. Org. Prep. Proceed. Int., 1995, 27, 129... 

Whereas Ullmann chemistry is limited to the coupling of aryl halides, a variety of species including aryl-, alkynyl-, alkenyl-, and alkylcopper species can be produced which are highly reactive toward other substrates. 

Nozaki-Hiyama-Kishi (NHK) reactions215,216 are well known and often employed as a useful method for the synthesis of natural products by coupling of allyl, alkenyl, alkynyl, and aryl halides or triflates with aldehydes. The organochromium reagents are prepared from the corresponding halides or triflates and chromium(ll) chloride, and are employed in polar aprotic solvents (THF, DMF, DMSO, etc.). Subsequently, it was found that nickel salts exhibited a significant catalytic effect on the formation of the C-Cr bond217,218 (Equation (19)). 

Pentafluorophenylcopper exhibits high reactivity towards a variety of organic substrates such as aryl, vinyl, alkynyl, allyl halides etc. [226,227,229,235-238] (Scheme 77). Similar to trifluorovinylcopper, pentafluorophenylcopper readily adds to hexafluoro-2-butyne to form the syn addition product, which can be quenched with electrophiles [230] (Scheme 78). 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

There is wide diversity in the nature of organohalogen compounds but, of necessity, we have restricted this chapter to alkyl, cycloalkyl, alkenyl, alkynyl, and aryl halides. Some of the chemistry of the carbon-halogen bonds already will be familiar to you because it involves the addition, substitution, and elimination reactions discussed in previous chapters. To some extent, we will amplify these reactions and consider nucleophilic substitution by what are called the addition-elimination and elimination-addition mechanisms. Subsequently, we will discuss the formation of carbon-metal bonds from carbon-halogen bonds. The latter type of reaction is of special value because compounds that have carbon-metal bonds are potent reagents for the formation of carbon-carbon bonds, as we will show later in this chapter. 

Alkenyl, alkynyl, and aryl halides, like alkyl halides, can be converted to the corresponding magnesium and lithium compounds. However, the reaction conditions, such as choice of solvent, can be critical. Bromoethene, for instance, can be converted to ethenylmagnesium bromide in good yield if the solvent is oxacyclopentane [tetrahydrofuran, (CH2)40] ... 

Secondary and tertiary dialkylcuprates, lithium dialkenyl-, and even diphenyl-cuprates, add in very good yields to the reactive propionaldehyde diethyl acetal. The syn addition products may be trapped with a variety of electrophiles such as alkyl, alkenyl, alkynyl and aryl halides. The method has been used for the synthesis of several natural products. Substituted alkynic acetals also react with lithium dialkylcuprates in ether to furnish stable dialkenylcuprates of type (128) which do not eliminate to the corresponding alkoxy allenes (129) if the temperature is maintained below -20 C.164-179... 

Various aryl, alkenyl and even alkylborane reagents of different reactivity can be used for coupling with aryl, alkenyl, alkynyl and some alkyl halides, offering very useful synthetic methods. The cross-coupling of aryl and heteroarylboronic acids with aryl and heterocyclic halides and triflates provide useful synthetic routes to various aromatic and heteroaromatic derivatives. Sometimes, the reaction proceeds in the... 

As organotin compounds (organostannanes) undergo smooth Pd-catalysed transmetallation, aryl halides react with a wide variety of aryl-, alkenyl- and alkylstannanes [139]. Coupling with allylstannane is the first example [140]. The reaction is called the Migita-Kosugi-Stille or Stille coupling. Aryl, alkenyl, allyl, alkynyl and benzyl... 

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