Palladium acetate olefination

Cupric Chloride can be used as a reoxidant in the vinyl acetate synthesis but other products are also produced. In fact, with increasing Cu(II) concentration, the side products can easily be made the major products 16>. The side products are chloro acetates and diacetates and they probably arise from a reaction of the palladium acetate-olefin adduct with cupric chloride or acetate. 

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. 

In most cases, the oxidative addition process consumes stoichiometric amount of Pd(OAc>2. One of the earliest examples of the use of palladium in pyrrole chemistry was the Pd(0Ac)2 induced oxidative coupling of A-methylpyrrole with styrene to afford a mixture of olefins 18 and 19 in low yield based on palladium acetate [28]. 

When furan or substituted furans were subjected to the classic oxidative coupling conditions [Pd(OAc)2 in refluxing HOAc], 2,2 -bifuran was the major product, whereas 2,3 -bifuran was a minor product [12,13]. Similar results were observed for the arylation of furans using Pd(OAc)2 [14]. The oxidative couplings of furan or benzo[i]furan with olefins also suffered from inefficiency [15]. These reactions consume at least one equivalent of palladium acetate, and therefore have limited synthetic utility. 

The electrochemical Wacker-type oxidation of terminal olefins (111) by using palladium chloride or palladium acetate in the presence of a suitable oxidant leading to 2-alkanones (112) has been intensively studied. As recyclable double-mediatory systems (Scheme 43), quinone, ferric chloride, copper acetate, and triphenylamine have been used as co-oxidizing agents for regeneration of the Pd(II) catalyst [151]. The palladium-catalyzed anodic oxidation of... 

Allylic acetoxylation with palladium(II) salts is well known however, no selective and catalytic conditions have been described for the transformation of an unsubstituted olefin. In the present system use is made of the ability of palladium acetate to give allylic functionalization (most probably via a palladium-x-allyl complex) and to be easily regenerated by a co-oxidant (the combination of benzoquinone-manganese dioxide). In contrast... 

Electron-rich heterocycles can also be coupled with olefins in the presence of a suitable palladium(II) catalyst. The oxidative coupling requires the use of a stoichiometric amount of palladium however, unless a suitable oxidising agent is added to the reaction. In an early example N-sulphonylated pyrrole was reacted with 1,4-naphthoquinone in the presence of an equimolar amount of palladium acetate to give the coupled product in good yield (6.92.).124... 

By using an olefin embedded into the parent molecule Stoltz developed the oxidative annulation of indoles. The optimal catalyst consisted of palladium acetate and ethyl nicotinate, and molecular oxygen was used as the oxidant in the process. The reaction proceeded equally well irrespective of the attachment point of the alkyl chain bearing the pendant olefin bond on the five membered ring, and the formation of five and six membered rings were both effective (6.95.),127... 

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... 

Palladium acetate has a trimeric ring structure (17) which is necessarily cleaved if a complex is formed. Both the a-olefin I and the internal olefin II follow a similar path in reacting with Pd3(OAc)6 to form trinuclear 1,2,3- and 2,3,4-/i3-hexenylpalladium complexes, Pd3-(C6Hii)2(OAc)4 (IVa and IVb, respectively) (Reaction 1). At 25°C in acetic acid this reaction is complete within 6 hrs, and if oxygen is absent, a second reaction follows in which the corresponding dimeric 1,2,3- and 2,3,4-/i3-hexenyl complexes Pd2(C6Hii)2(OAc)2 (Va and Vb, respectively) appear (Reaction 2). 

Benzoquinone has been used as an alternative oxidizing agent to oxygen in the oxidation of olefins catalyzed by palladium acetate (1). Presumably it has the same role as a regenerating agent in oxidizing some... 

Materials. Palladium acetate was prepared by oxidizing palladium black in acetic acid by 02 or by nitric acid (20). Material from nitric acid oxidation was crystallized five times or more before use, or more often, was purified by the following procedure. Finely powdered palladium acetate was made into a paste with sulfuric acid and digested at 140°-150°C for 30 min. Palladium (II) was thus converted into palladium sulfate, and crucial impurities were destroyed. Palladium sulfate was dissolved in water. After the sulfuric acid was neutralized, the addition of excess acetic acid precipitated purified palladium acetate. Oxi-dizable impurities were removed from acetic acid by repeated fractionation from CrOa and KMn04 solutions. Olefins were treated with alumina before use to remove peroxides. The reproducibility of the rate data was used as a test of the purity of reagents since the results were erratic when inadequate precautions had been taken. 

The olefinic substitution reaction may also be effected in some instances by using a palladium(II) salt and an aromatic compound instead of an organic halide. Palladium(II) salts are apparently able to metallate some aromatic hydrocarbons directly. The reaction succeeds best with aromatics activated with electron-supplying substituents producing, with certain olefinic compounds, vinylically substituted products. For example, benzene and styrene with palladium acetate in boiling acetic acid produce stilbene in 90% yield (37). 

Palladium acetate triarylphosphine complexes catalyze the addition of vinylic groups from vinylic halides to olefinic compounds in the presence of amines. Conjugated dienes are major products from 0,/3-unsaturated acids, esters, or nitriles while unactivated olefinic compounds react best in the presence of secondary amines where allylic amines are major products. The reactions are usually regio- and stereospecific. The synthetic utility of the reaction is illustrated with a wide variety of examples. 

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],... 

A study of the olefin oxidation catalyst system, palladium acetate-MOAc (M = Li or Na), has shown that in the absence of acetate ion, Pd acetate-acetic acid exists as the trimeric species [Pd3(OAc)6].32 Reaction with MOAc is not instantaneous, and u.v.-visible spectra indicate an initial equilibrium involving trimer - dimer (9). When M = Na conversion into dimer is complete at 0.2M-NaOAc. Further addition of... 

The palladium acetate addition to 1-olefins in acetic acid solution is predominately of the Markovnikov type producing ketone enol esters 14>. 

The direction of the addition to 1-olefins is largely anti-Markovnikov if the reaction is carried out in a solvent mixture of 70% dimethylsul-foxide-30% acetic acid 14> or if substantial amounts of acetate salts are added to the acetic acid solvent 15>. The reasons for this effect are not certain the change in direction of addition may result from the fact that pure palladium acetate is highly associated in acetic acid solution... 

The details of the cupric salt reaction with the palladium adduct are not clear. Exchange to form a cupric alkyl is one possibility or complex formation,"probably with chloride bridges between the palladium adduct and cupric chloride, may occur with subsequent anion shift from palladium to carbon or perhaps an Sn2 displacement of the complex metal group by an anion may occur. Rearrangements producing 1,3 and 1,4 substituted products from linear olefins have also been observed. For example, 1-butene produced several percent of 1,3- and 1,4-chloro acetates and diacetates under the reaction conditions used 16>. "Hydrido-palladium acetate or chloride" -complexes would seem to be likely intermediates in these arrangements. 

Similar stereochemical results have been obtained with different starting olefins and with the aliphatic palladium compound, "carbo-methoxypalladium acetate prepared in situ from carbomethoxymercuric acetate 27> and palladium acetate 24>. The latter reagent allows unsaturated esters to be prepared from olefins. 

In the reaction of "carbomethoxypalladium salts with olefins, there is a marked tendency to product unsaturated esters in which the double bond is not conjugated with the carbonyl. The reaction of carbomethoxy palladium acetate with a-methylstyrene produced an 86% yield of unsaturated esters of which 96% was the non-conjugated isomer, methyl 3-phenyl-3-butenoate and only 4% was the imws-conjugated product 24>. 

The presence of chelating groups in those complexes is necessary to stabilize the intermediate aryl-palladium complex for isolation but it does not seem necessary to cause palladation. The chelating group does, however, tremendously accelerate the palladation. Aromatic compounds reactive to electrophilic substitution apparently undergo palladation with palladium acetate in acetic acid solution fairly readily at 100 °C or above. Of course, the arylpalladium acetates presumably formed, are not stable under these conditions, and they decompose very rapidly into biaryls and palladium metal 34,35,36) ag do aryl palladium salts prepared by the exchange route 24>. If the direct palladation is carried out in the presence of suitable olefins, arylation can be achieved, so far, however, only in poor yields, arid with concurrent loss of stereospecificity and formation of isomers and other side products 37.38). 

For cases in which vinylation with higher olefins has been studied, conflicting results have been reported. In one case, it has been reported (29) that olefins give predominantly 2-substitution—e,g.y l-penten-2-yl acetate (I) from pentene when a palladium acetate-acetic acid system is used. On the other hand, a buffered (sodium acetate) acetic acid solution of palladium chloride has been reported (58) to give 1-substitu-tion—e.g., 2-hexen-l-yl acetate (II) from hexene. Propylene has been... 

The use of palladium and ruthenium as halogen-free carbonylation catalysts has been studied intensively by Shell. The catalysts were principally designed for the carbonylation of olefins in the presence of alcohols in order to yield carboxylic esters [26], but work also well for the synthesis of carboxylic acids or anhydrides. The latter are formed when the reaction is conducted in an acid as a solvent [27]. The palladium systems typically consist of palladium acetate, tertiary phosphines, and strong acids such as mineral acids or acids with weak or noncoordinating anions such as p-toluenesulfonic acid. Remarkable activities are achieved when aromatic phosphines that carry pyridines as substituents are... 

As mentioned earlier, palladium, rhodium, and platinum catalysts lead to superior regioselectivities because they work under milder reaction conditions (20-80 °C, 0.1-1 MPa CO) [11], e.g., bimetallic catalysts based on tin(II) chloride and either platinum or palladium complexes afford linear esters in up to 98 % selectivity [12]. In addition, catalyst systems with preference for branched isomers are known. A recent example employed palladium acetate immobilized on montmorillonite in the presence of triphenylphosphine and an acid promoter for the hydroesterification of aryl olefins (eq. (3)). The reaction is totally regiospecific for the branched isomer of aromatic olefins, while aliphatic olefins afford branched chain esters only regioselectively with n/i = 1 3 [13]. 

Palladium-based catalysts also bring about cyclopropanations in high-yield. With palladium acetate/CHjNj, styrene , unactivated terminal olefins strained olefins , 1,3-dienesan enamine , as well as a,3-unsaturated carbonyl compounds have been cyclopropanated (Table 1). Contrary to an earlier report, the reaction also works well with cyclohexene if the conditions are chosen appropriately it seems that the notniyst is rapidly deactivated in the presence of this olefin >. Trisubstituted a,p-unsaturated carbonyl compounds were found to be unreactive, and the same is true for the double bonds in diethyl fumarate, maleic anhydride, coumarin and 1,3-dimethyluracil. Whereas the latter two were totally unreactive, [3-1-2] cycloaddition of diazomethane gave pyrazolines in the former two cases. The last entry of Table 1 shows that an allyl alcohol function can still be cyclopropanated, but methylene insertion into the O—H bond is a competing process. 

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. 

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