Heck alkyne coupling

In addition, the application of Jeffery s conditions by Sinou and co-workers, with extra triphenylphosphine and tetrabutylammonium hydrogensulfate, confirmed that Cul is not essential to success in alkyne coupling reactions [24], Moreover, they reported the most efficient coupling of bromoanisole with propargyl alcohol in 81% yield. These results prompted the authors to apply these conditions in a cascade reaction, consisting of an intermolecular Heck reaction followed by cyclization of the intermediate cr-complex (Eq. 9). The product, which is a mixture of (E) and (Z) stereomers (approximately 1 1), was sometimes contaminated with a by-product resulting from aromatization, especially for longer reaction times. 

The synthesis commenced with a site-selective Heck-Sonogashira coupling of the easily prepared indole 174 and known alkyne 175. Selective reduction of the resulting alkyne 176 to the corresponding cis olefin followed by a two-step... 

They explored this strategy for the synthesis of chartelline C (145) and it was started by taking indole 156 and alkyne 157, which after Heck-Sonogashira coupling yielded compound 158 (Scheme 14) [74],... 

Indole and isoquinolone nuclei are prominent structural units frequently found in numerous natural products and pharmaceutically active compounds. Thus, the search for new methodologies to obtain these scaffolds with different substitution patterns is a current major objective in organic synthesis. Similar to benzofuran synthesis, Aluraez et al. observed that the palladium-catalyzed cascade intramolecular alkyne aminopaUadation/intermolecular Heck-type coupling reaction under oxidative conditions is an efficient methodology for the synthesis of indole 217 and isoquinolone 219 derivatives, starting from readily available aniline 216 or benzamide 218 substrates and functional alkenes [77] (Scheme 6.60). 

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

The Heck-Cassar-Sonogashira-Hagihara system, which couples terminal alkynes and vinylic or aromatic halides in an amine solvent, typically piperi-... 

Attempts to use in the alkynylation reaction not tin-substituted alkynes, but to couple 26 directly under the conditions developed by Heck, Cassar, Sono-gashira, and Hagihara, surprisingly enough gave rise to the formation of the corresponding amino-substituted cyclobutadiene complex 30 in good yields. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Using Pd-mediated cross-coupling reactions, such as Suzuki, Heck, and Sonoga-shira- Hagihara reaction, researchers efficiently constructed a library of 151 coumarin derivatives from eight 3-bromocoumarins cross-coupled with ten aryl/heteroaryl boronic acids, ten alkenes, and ten alkynes (Fig. 4). 

Zhao and Larock have described the synthesis of carbazoles, indoles, and dibenzofurans 118 via a Ic type cyclization that follows a sequence of Pd-catalyzed cross-coupling of alkynes and aryl iodides 116, then nitrogen-directed palladium migration to an arylpalladium intermediate 117 that undergoes an intramolecular Mizoroki-Heck ring closure <06JOC5340>. 

Diazonium salts are another useful source of free radicals, and the formation of the reactive species can be achieved by reductive electrolysis or direct treatment with diazonium tetrafluoroborate salts [39]. By this route, several aryl derivatives could be introduced onto the nanotube sidewalls [40]. Aryl groups bearing halogen or alkyne functionalities are particularly interesting as they can be further reacted in Pd-catalyzed coupling reactions (Suzuki, Heck) or in click chemistry reactions to create products with great potential in materials science [41]. 

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