Heck reaction palladium acetate

A novel route to indoles and quinolines has been developed by sequential Wiltig and Heck reactions <96CC2253>. Thus, treatment of o-bromo- or iodo-lV-lrifluoroaceiylanilines (86) with a stabilized phosphorane affords the corresponding enamines 87 as a mixture of isomers. Cyclization to 88 is effected by heating with palladium acetate, tri phenyl phosphine, and bu.se. 

In 1975, Heck described the first non-catalytic example of this reaction, nsing organoboronic acids as precursors and stoichiometric amounts of palladium acetate... 

In a recent article by Botella and Najera, controlled mono- and double-Heck arylations in water catalyzed by an oxime-derived palladacycle were described [22], When the reaction was carried out under microwave irradiation at 120 °C in the presence of dicyclohexylmethylamine with only 0.01 mol% of palladium catalyst (palladium acetate or palladacycle), monoarylation took place in only 10 min with a very high turnover frequency (TOF) of > 40000 (Scheme 6.3). As regards diarylation, 1 mol% of the palladacycle catalyst and 2 equivalents of iodobenzene had to be utilized to obtain moderate to good yields of diarylated product. Whereas microwave heating at 120 °C provided a 31% yield after 10 min, a 66% isolated yield of product was obtained by heating the reaction mixture under reflux for 13 h at 100 °C. Here, the... 

Palladium catalyzed reaction of aryl halides and olefins provide a useful synthetic method for C-C bond formation reaction [171, 172], The commonly used catalyst is palladium acetate, although other palladium complexes have also been used. A sol-vent-free Heck reaction has been conducted in excellent yields using a household MW oven and palladium acetate as catalyst and triethylamine as base (Scheme 6.51) [173], A comparative study revealed that the longer reaction times and deployment of high pressures, typical of classical heating method, are avoided using this MW procedure. 

Fluorous-derivatized phosphines have also been used for Heck reactions in scCC>2 together with palladium acetate [7]. The fluorous groups improve the solubility of the catalyst in the SCF compared to nonfluorous ligands. An example of a Heck reaction that uses a fluorous-derivatized phosphine to improve the solubility of a Pd(OAc)2 catalyst is shown in Scheme 10.5. 

Domino-Heck Reactions-General Procedure 5.6 mg (25 pmol) of palladium(II) acetate and 55 pmol of the arsine ligand were dissolved in 3 ml of dry dimethyl formamide and the solution was stirred at 65°C (40°C for trimethylsilylacetylene) for 15 mitt Then, 127 mg (1.35 mmol) N-Benzoyl-2-azabicyclo[2.2.1]hept-5-en-3-one, 1 mmol of the aryl compound. Four hundred and eighty-eight microliters (3.50 mmol) of triethylamine, and 3.00 mmol of the phenylacetylene (or silylmethyl-acetylene) were added rapidly in one portion. The mixture was heated at the same temperature for 24 h. After cooling down to room temperature 50 ml of brine were added, the reaction mixture was extracted with ethyl acetate and dried over MgSO. The solvent was evaporated, the residue purified by column chromatography (n-Hexan-Ethyl acetate 4 1). 

As detailed elsewhere, the fluorous palladacycle acetates and hahdes 7 and 8 were synthesized [38,39]. These feature three Rfg ponytails, and were poorly soluble in common organic solvents at room temperature, and insoluble in DMF. However, they were very soluble in DMF at higher temperatures. All were effective catalyst precursors for Heck reactions (100-140 °C), and precipitated (as the halides) upon cooling. However, a number of control experiments established that 7 and 8 served as steady-state sources of colloidal palladium nanoparticles, formed anew with each cycle imtil the palladacycles were exhausted. These, or low-valent Pd(0) species derived therefrom, were the true catalysts. 

The Heck reaction of dihydroindoles produces a mixture of cyclized products, the ratio of which can be controlled by varying the reaction conditions < 1998CEJ1554>. Hence, the < a ti-product is produced exclusively using palladium acetate as catalyst in the presence of silver carbonate and is isomerized to the endoA oms. i on exposure to camphor-sulfonic acid (CSA) at room temperature (Scheme 11). 

A twofold intramolecular Heck reaction of the dibromobenzene derivative 19 has been used to construct the heptacyclic skeleton 20 of cephalostatin analogs. This reaction required a precise control of the reaction time and temperature. The conversion proceeded best with a catalytic amount of the palladacycle from tris(< -tolyl)phosphine and palladium acetate, and gave exclusively (in 80% yield) the heptacycle 20 with an unusual m-annelation of the two newly formed rings (Scheme 10). ... 

The Heck coupling is also efficient in the formation of pyrane derivatives. By starting from the appropriately substituted 1,3,5-tribromobenzene derivative, three fused pyrane rings were constructed in the same reaction. The triple Heck reaction in the presence of palladium acetate and triphenylphosphine led to the formation of the tetracyclic product in good yield accompanied by a minor amount of the tricyclic intermediate(4.12.).13... 

The use of the heteroaryl Heck reactions extends beyond fine chemicals synthesis. Polythiophenes were prepared starting from 3-octyl-2-iodotiophene by heating in the presence of palladium acetate and tetrabutylammonium chloride (6.91.),122 The arylation of benzothiophene has also been achieved under the same conditions.123... 

The Heck reactions depicted so far all involve the coupling of halopyridines and other olefins. The alternate approach, coupling of a vinylpyridine with an aryl halide is also feasible, although less commonly employed. 4-Vinylpyridine was coupled successfully with diethyl 4-bromobenzylphosphonate (7.50.) in the presence of a highly active catalyst system consisting of palladium acetate and tn-o-tolylphosphine to give the desired product in 89% yield, which was used for grafting the pyridine moiety onto metal oxides.70... 

Polystyrene-bound secondary aliphatic amines and /V-alkyl amino acids can be ally-lated by treatment with a diene and an aryl iodide or bromide in the presence of palla-dium(II) acetate (Entry 14, Table 10.3). As the diene, 1,3-, 1,4-, and 1,5-dienes can be used, and, besides aryl halides, heteroaryl bromides have also been successfully used [63], This remarkable reaction is likely to proceed via the formation of an aryl palladium complex, with subsequent insertion of an alkene into the C-Pd bond. The resulting organopalladium compound does not undergo ( -elimination (as in the Heck reaction), but isomerizes to an allyl palladium complex, which reacts with the amine to give the observed allyl amines. 

It has been shown that combination of bromoallylation reaction and Heck cyclization is a useful methodology for the preparation of a variety of fused bicyclic (3-lactams of nonconventional structure [95], Starting from acetates 164 and using palladium acetate as the palladium source, DMF as solvent, potassium carbonate as base, and triphenylphosphine, the reaction occurred. The reaction conditions were further optimized and typical results for the preparation of bicyclic (3-lactams 165-168 are summarized in Schemes 57. 

Heck reaction of 5-iodo-2,4-dimethoxypyrimidine and the furanose 3-deoxyglycal 147 with catalytic quantities of palladium acetate gives a mixture of the 2,3- and 3,4-enes 148 and 149 (Scheme 15). With triphenylarsine also present the latter product is favored, whereas with triphenylphosphine the 2-ene is produced without its isomer.164 Further examples of this type of chemistry have been reviewed by Daves.118... 

Stereocontrolled access to bicyclic /3-lactams has been achieved by application of the Heck reaction to bromoalk-enes. Cyclization of the 3,4-disubstituted azetidinone 287 (R = H) was achieved using palladium(n) acetate, triphe-nylphosphine, and potassium carbonate in DMF but two products 288 (R = H) and 289 were obtained in 21% and 27% yield, respectively. When the allyloxy group had a methoxycarbonyl substituent in 287 (R = G02Me) only one product 288 (R = C02Me) was produced in 47% yield <2005JOC2713>. 

A nonclassical substrate for the Heck reaction is 2,3-epoxycyclohexanone. The reactivity of this molecule under Heck coupling conditions is most likely attributed to its in situ isomerization to 1,2-cyclohexanedione. The 1,2-diketone subsequently reacts with aryl bromides as an olefin via the enol tautomer. Thus, within 5 to 30 min of directed microwave heating of the aqueous PEG mixture, up to 13 different C3-arylations were conducted using less than 0.05 mol % palladium acetate and no phosphine ligand (Scheme 12) [51]. 

The useful and selective reactivity of arylboronic acids makes them favorite building blocks for many modern organic chemistry applications. Arylboronic acids also serve as highly useful arylpalladium precursors in palladium(II)-catalyzed oxidative Heck reactions. Andappan et al. developed a microwave-accelerated protocol for oxidative Heck couplings using cop-per(II) acetate as the palladium reoxidant [52]. The method proved to be... 

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

Palladium/silver-catalyzed Heck reactions have usually involved vinyl or aryl halides and alkenes, but these reaction conditions were also extended to allenes. Indeed, Zenner and Larock65 showed that simple alkyl allenes readily reacted with aryl and vinyl iodide derivatives in the presence of palladium acetate or chloride and silver phosphate. Moreover, the reaction could be rendered asymmetric using chiral ligands the best one was a bisoxazolidine derivative (Scheme 10.37). 

Fig 16 34 Heck reactions- For a Heck reaction to occur, catalytic amounts of (usually) palladium(II) acetate—though... 

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