Heck 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. 

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... 

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... 

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]. 

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). 

Iodination (I2/NaOH) of l,6-naphthyrid-5-one (47) gives the iodo derivative (48) (70% yield). This compound is converted to 5-chloro-8-iodo-l,6-naphthyridine (49) by the action of phosphorus oxychloride (64% yield). Heterocycle (49) undergoes a Heck reaction with ethyl acrylate in the presence of palladium acetate as a catalyst giving compound (51) (47% yield). Similarly, heterocycle (50) (obtained in 98% yield by treating compound (49) with sodium methoxide) gives ester (52) (88% yield) in a Heck reaction <86CPB2018>. 

The reaction of allylic alcohols and aryl halides in the presence of a palladium catalyst has been used in the past to prepare various 0-arylal-dehydes. The procedure described here is essentially that of Heck and Melpolder.3 A similar reaction has been carried out with bromobenzene and 2-methyl-2-propen-l-ol in hexamethylphosphoric triamide (HMPT) as solvent with sodium bicarbonate as base. A variety of other bases have also been used.4 2-Methyl-3-phenylpropanal has been prepared by reacting palladium acetate and phenylmercuric acetate with 2-methyl-2-propen-l-ol.5... 

Alkenyl, Alkynyl, Aryl and Heteroaryl Acids. Treatment of readily accessible (E)- and (Z)-alkyl and aryl substituted vinyl boronates (196) with triethyl phosphite in the presence of lead diacetate results in their stereospecific transformation into (E)- and (Z)-vinylphosphonates (197) (Scheme 53). ° Palladium acetate catalysed Mizoroki-Heck reaction of arylboronic acids (198) with diethyl vinylphosphonates (199) is an effective synthetic approach to... 

Evans J, O Neill L, Kambhampati VL, Rayner G, Turin S, Genge A, Dent AJ, Neisius T (2002) Structural characterisation of solution species implicated in the palladium-catalysed Heck reaction by Pd K-edge X-ray absorption spectroscopy palladium acetate as a catalyst precursor. J Chem Soc, Dalton Trans 10 2207... 

Heck-type vinylations of alkynic halides proceed only under solid-liquid phase-transfer conditions. These mild conditions allow the reaction to be performed with thermily unstable substrates. Thus, methyl ( )-enynoates can be obtained from the reaction of 1-iodoalkynes with methyl 2-propenoate in DMF at room temperature in the presence of potassium carbonate, tetrabutylammonium chloride and a catalytic amount of palladium acetate (Scheme 36)." ... 

An interesting application of the Fujiwara-Moritani/oxidative Heck reaction for the synthesis of benzo furans was recently reported by the Stoltz lab [31]. A variety of allyl phenyl ethers (all containing electron-rich aryl components) react with 10 mol% palladium acetate, 20 mol% ethyl nicotinate, 20 mol% sodium acetate, and one equivalent of benzoquinone at 100°C to provide benzofurans in 52-79% yield (e.g. 16—>17). The mechanism of this transformation begins with arene palladation of Pd(II) followed by olefin insertion, p-hydrogen elimination, and olefin isomerization to the thermodynamically favored benzofuran product. The resulting Pd(0) species is then oxidized to Pd(ll) thus regenerating the active catalyst. 

In the search of new non-peptide glycoprotein GPIIb/GPIIIa antagonists, heterocyclic scaffolds such as oxazolepiperidine have been explored. Such framework has both acidic and basic functionalities, which may confer the pharmacological properties to the desired molecule. The Heck reaction of bromooxazolopyridines 104 with methyl acrylate in the presence of palladium acetate afforded methylpropenoate-oxazolopyridines 105 in 70 and 88% yields, respectively [60]. 

At the early stage of Heathcock s biomimetic total syntheses of discorhabdins [108], a 5-ejco Heck cyclization was employed for the synthesis of 3,6,7-functionalized indole. As highlighted in Scheme 42, when precursor 237 was exposed to catalytic palladium acetate, tri-o-tolylphosphine, and stoichiometric base, indole 238 was smoothly produced in 89% yield. Subsequently, the total syntheses of discorhabdin C (239) and discorhabdin E (240) were accomplished using indole 238 as the common intermediate. 

The Heck reaction has been widely used for the synthesis of many natural and unnatural products. The Heck reaction catalyzed by palladium acetate in water using a water-soluble ligand has been employed for the synthesis of clavicipitic acid (Scheme 5.24). 

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