Terminal alkynes, cross-coupling with

In tMs section, Pd-catalyzed homocoupling of terminal alkynes, cross-coupling of terminal alkynes with internal alkynes, and cross-coupling of terminal alkynes with allenes will be discussed. All three types of reactions involve (i) activation of the C—bond of a terminal alkyne, (ii) alkynylpalladation of another molecule of alkyne or allene, and (iii) reductive elimination or protonation to produce a conjugated enyne. For alkynylpallada-tions of allenes followed by trapping with nucleophiles, see Sect IV.7. 

The alkynyl iodide 359 undergoes cross-coupling with a terminal alkyne to give the 1,3-diyne 360[264]. No homocoupling product is formed. This reaction offers a good synthetic method for unsymmetrical 1,3-diynes. 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

Kotschy et al. also reported a palladium/charcoal-catalyzed Sono-gashira reaction in aqueous media. In the presence of Pd/C, Cul, PPI13, and z -Pr2NH base, terminal alkynes smoothly reacted with aryl bromides or chlorides, such as 2-pyridyl chloride, 4-methylphenyl bromide, and so on, to give the expected alkyne products in dimethyl-acetamide (DMA)-H20 solvent. Wang et al. reported an efficient cross-coupling of terminal alkynes with aromatic iodides or bromides in the presence of palladium/charcoal, potassium fluoride, cuprous iodide, and triph-enylphosphine in aqueous media (THF/H20, v/v, 3/1) at 60°C.35 The palladium powder is easily recovered and is effective for six consecutive runs with no significant loss of catalytic activity. 

The related cyclization of 2-ethynylanilines 67 also represents one of the usefiil methods for the synthesis of 2-substituted indoles since the precursors are easily prepared from 2-haloanilines 66 by Pd-catalyzed cross-coupling with terminal alkynes. Althou cyclizations of such alkynes are normally effected using Cu(I) or Pd(II) species, Sakamoto showed that in the absence of such metals, base catalysis (e.g., NaOEt) alone can accomplish the same goal. This author now reports that tetrabutylammonium fluoride (TBAF) is capable of inducing cyclization to the indoles 68 without affecting functionalities such as bromo, cyano, ethoxycarbonyl, and ethynyl <99JCS(P1)529>. 

Cross-coupling with Terminal Alkynes to Form Alkenyl- and Arylalkynes... 

Scheme 10.7 depicts the synthesis of an OPE3 one-terminal wire compound by repeated Sonogashira cross-couplings [13c]. The synthesis takes advantage of the more reactive iodide as compared with the bromide, which allows for stepwise scaffolding. Thus, two concomitant Pd-catalyzed cross-couplings of 23 produced 24. The terminal alkyne obtained after desilylation was subsequently cross-coupled with 1 to afford 25. 

Triiodobenzene (69) serves as a suitable core for the synthesis of three-terminal OPEs. Thus, a three-fold cross-coupling with the alkyne 70 produced 71 (Scheme 10.23) [13c],... 

Haloboration of terminal alkynes yielded stereodefined (Z)-2-halo-l-alkenylboron compounds e.g., 114, 115 that allowed further functionalization of the resulting C-Br or G-B bond. 2,2-Disubstituted-l-alkenylboronic esters were stereoselectively obtained when the haloboration was followed by cross-coupling with 1-alkynylzinc chlorides (Equation (18)).192 The iodoboration-conjugate addition sequence gave alkenyl iodides that were used as intermediate for the total synthesis of deoxyepothilone derivatives (Equation (19)).193-195... 

Haloboranes add to terminal alkynes in a cis /in-Markovnikov manner however, the bromoboration of acetylene itself exceptionally provides a trans adduct [28] (eq (17)). A sequence of haloboration with boron tribromide and then cross-coupling with organozincs is useful for a formal carboboration of alkynes with various organic groups. Addition of boron triboromide to allene is convenient for the synthesis of (2-bromo-2-propeny])borate [29] (eq (18)). 

Alkyne cross-coupling reactions over the last 25 years have become one of the most valuable assets in the synthetic chemist s toolbox. The now famous Sonogashira coupling (50, 114) of terminal alkynes with aryl or vinyl halides is readily achieved with a palladium catalyst, a copper(l) cocatalyst, and amine base. In the catalytic cycle (Scheme 14a), copper-and palladium-alkyne complexes are the key intermediates that lead to coupling of R and R units via the alkyne. Analogously, the Stille coupling... 

Several syntheses of dihydropyran-2-ones use smaller ring systems as precursors. A direct conversion of cyclopropylidene acetates into 4-halo-5,6-dihydropyran-2-ones occurs on treatment with Cu(II) halides. The products undergo a Pd-catalysed cross coupling with terminal alkynes <04JOC839>. 

Cross-coupling of acetylenes with aryl halides E)-alkenylarenes. (E)-Atkenyl-zirconium compounds (1), obtained by hydrozirconation of terminal alkynes, react smoothly with aryl bromides and iodides in the presence of 10 mole % of Nl[P(CeH5)3]4 to form (E)-alkenylarenes (2) in yields generally of 70-95%. ... 

Recently, the sequential, one-pot Pd-catalyzed coupling of an o-halophenol and a terminal alkyne, followed by cross-coupling with a vinylic halide has provided an efficient approach to a complex benzofuran-containing natural product (Eq.6) [27]. 

The Pd-catalyzed coupling of o-haloanilines and terminal alkynes tends to produce either the 2-(l-alkynyl)aniline or mixtures of the alkynylanilines and the corresponding indoles [17,18]. However, iV-benzyl-2-iodoaniline has recently been cross-coupled with terminal alkynes to afford the corresponding ben-zylindoles using a Pd zeolite catalyst (Eq. 14) [39]. One can also employ stoichiometric amounts of copper acetylides to effect this transformation [22-24]. 

Cross-Coupling with Terminal Alkynes the Sonogashira Reaction.257... 

Terminal alkynes may be deprotonated with LDA and transmet-allated with zinc to undergo palladium-catalyzed cross-couplings with aryl electrophiles (Scheme O... 

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