Palladium formation with alkynes

Palladium-Catalyzed Carbon-Heteroatom Bond Formation with Alkynes... 

Palladium-catalysed C-C bond formation under Heck reaction conditions, which normally requires anhydrous conditions and the presence of copper(I) salts, is aided by the addition of quaternary ammonium salts. It has been shown that it is frequently possible to dispense with the copper catalyst and use standard two-phase reactions conditions [e.g. 18, 19]. Tetra-/i-butylammonium salts catalyse the palladium-catalysed reaction of iodoarenes with alkynes to yield the arylethynes in high yield [20, 21], whereas the reaction with 3-methylbut-1 -yn-3-ol (Scheme 6.30) provides a route to diarylethynes [22]. Diarylethynes are also formed from the reaction of an iodoarene with trimethylsilylethyne [23], Iodoalkynes react with a,p-unsaturated ketones and esters to produce the conjugated yne-eneones [19],... 

C-M bond addition, for C-C bond formation, 10, 403-491 iridium additions, 10, 456 nickel additions, 10, 463 niobium additions, 10, 427 osmium additions, 10, 445 palladium additions, 10, 468 rhodium additions, 10, 455 ruthenium additions, 10, 444 Sc and Y additions, 10, 405 tantalum additions, 10, 429 titanium additions, 10, 421 vanadium additions, 10, 426 zirconium additions, 10, 424 Carbon-oxygen bond formation via alkyne hydration, 10, 678 for aryl and alkenyl ethers, 10, 650 via cobalt-mediated propargylic etherification, 10, 665 Cu-mediated, with borons, 9, 219 cycloetherification, 10, 673 etherification, 10, 669, 10, 685 via hydro- and alkylative alkoxylation, 10, 683 via inter- andd intramolecular hydroalkoxylation, 10, 672 via metal vinylidenes, 10, 676 via SnI and S Z processes, 10, 684 via transition metal rc-arene complexes, 10, 685 via transition metal-mediated etherification, overview,... 

The alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

Generally, the Sonogashira coupling reaction is achieved by a palladium-copper catalyzed reaction of aryl or vinyl halide and terminal alkyne [70-72], The presence of the copper co-catalyst is an obstacle, however, towards the metallodendritic approach of the system. In this context, only a few examples of copper-free procedures have been reported [73-77], involving for instance, in situ Pd(0) complex formation with bulky phosphines [78]. 

Another useful route involving formation of two bonds is based on palladium-catalyzed annulation of 2-iodoanilines with alkynes. As the use of trimethylsilyl acetylenes leads to regioselective formation of indoles bearing a TMS group at C-2 <1998JOC7652>, this approach has proven to be useful in the synthesis of optically active tryptophans <1999TL657>. In a typical example, the substituted o-iodoaniline 364 and the acetylene 365 were efficiently converted to the indole 366 (Equation 102), which could thereafter be transformed into 5,6-dimethyl-L-tryptophan <2001JOC4525>. 

There has been a theoretical study of the reaction of arenediazonium cations with azide anions, which yields arylazides. No evidence for the formation of arylpen-tazoles was found. Arenediazonium salts have been identified as intermediates in the palladium-catalysed Sonagashira reaction of arylamines with alkynes to give arylalkynes. Palladium catalysis has also been used in the synthesis of diarylheptanols by the reaction of 4-hydroxybenzenediazonium ions with dihydropyrans. ... 

Oxidative addition of certain stannanes to Pd(0) complejKS is also possible. Thus, aUcynylstannanes have been shown to react with Pd(0) complexes [207, 208). In addition, the Pd(0)-catalyzed reaction of allylstannanes with alkynes has been found to afford aUylstannylation products 31 (Scheme 1.23) [209]. A likely mechanism involves oxidative addition of the allylstannanes to Pd(0) to give (ri -allyl) palladium complexes 32 (L = alkyne) (Scheme 1.23). In this transformation, the usually nucleophilic allylstannanes behave as electrophiles. Complexes of type 32 are probably formed by transmetallation of (T) -aUyl)palladium complexes with hexamethylditin [210]. An oxidative addition to form complexes 32 has been proposed in the Pd(0)-catalyzed carboxylation of allylstannanes with COj [211]. Although compleres 32 have not been isolated as stable species, work on the intramolecular reachon of allylstannanes with alkynes and theorehcal calculations give support to the formation of these complexes by the oxidahve addition of allylstarmanes to Pd(0) [212]. 

Pd-catalyzed hydrogenolysis of allylic compounds with formates is an efficient and mild method. The hydride generated from the palladium formate attacks the more substimted side of the allylic system to give less substituted olefins in contrast to the case with other hydride sources. Pd-catalyzed hydrogenolysis of propargylic compounds affords either aUenes or alkynes depending on the structure of the propargylic compounds. 

Cyclopalladation products react with alkynes to be inserted into the palladium-carbon bond, followed by reductive elimination of Pd(0), which leads to the formation of a C-N bond. Then the heterocyclic compound is yielded as shown in eq. (20.62) [195,213]. 

Catalytic carbopalladation is a ubiquitous process and alkynes are viable substrates. Alkenyl tellurides couple efficiently with alkynes with retention of the double bond geometry. Relatively large amounts of palladium catalyst are required.Oxidative dimerization of monoterpenes has been assumed to involve alkenylpalladium(ii) intermediates. Alkenylpalladium(ii) and di(alkenyl)palladium(iv) complexes have been put forward as intermediates in a similar reaction of halogenoterpenes. The subject has been reviewed concerning the formation of heterocycles by intramolecular cyclization of intermediate alkenylpalladium intermediates. ... 

The following discussion focuses on the synthesis of aromatic heterocycles where a key palladium- or copper-catalyzed aryl halide (or equivalent) amination, etherification or thioetherification process is employed. Annulative routes utilizing anilines and related compounds with alkynes (Larock type) are also considered. Routes that do not lead to aromatic products or that rely on the functionalization of preexisting heterocycles have been discounted. Similarly, the synthesis of heterocycles via TT-allylpalladium chemistry or intramolecular cyclization of palladium Tr-olefin and TT-alkyne complexes is not featured. The discussion is structured predominantly around the type of bond being formed (C—N, C—O, or C—S) and is classified further by heterocycle type. Intramolecular and intermolecular C—X bond formations as well as tandem catalytic processes leading to aromatic heterocycle products are all discussed. 

Similar 1 1 and/or 1 2 coupling reactions of benzamides with alkynes were reported by Guimond s, Rovis s, and Li s groups [35]. Later, ruthenium- [36], palladium- [37], and nickel-catalyzed [38] versions for isoquinolinone synthesis were disclosed. Shi et al. reported similar lactam formation through dehydrogenative annu-lation of an indolecarboxamide 91 with 2c under palladium catalysis (Scheme 25.45) [39],... 

It was found [99JCS(PI )3713] that, in all cases, the formation of the deiodinated products 38 and 39 was accompanied by formation of the diynes 40 which were isolated in 60-90% yield. The authors believed that the mechanism of deiodination may be represented as an interaction ofbis(triphenylphosphine)phenylethynyl-palladium(II) hydride with the 4-iodopyrazole, giving rise to the bisftriphenylphos-phine)phenylethynyl palladium(II) iodide complex which, due to the reductive elimination of 1 -iodoalkyne and subsequent addition of alk-1 -yne, converts into the initial palladium complex. Furthermore, the interaction of 1-iodoalkynes with the initial alkyne in the presence of Cul and EtsN (the Cadiot-Chodkiewicz reaction) results in the formation of the observed disubstituted butadiynes 40 (Scheme 51). 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

Hydroboration of alkenes or alkynes followed by cross-coupling with organic electrophiles provides a straightforward method for the carbon-carbon bond formation (Scheme 1-19). The hydroboration of thioalkynes with catecholborane in the presence of a nickel or palladium catalyst yields P-(aLkylthio)-l-alkenylboronates (72a)... 

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