Heck reaction palladium acetate - oxidants

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... 

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... 

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. 

Intramolecular Heck reactions are particularly efficient and have been used considerably in organic synthesis.In situ reduction of palladium acetate and oxidative addition of the resulting palladium(O) into the aryl iodide 210 gave an... 

Direct functionalization of the C2 position of thiophene can be accomplished through an oxidative-Heck reaction employing palladium(II) acetate in the presence of silver carbonate. The resulting products are obtained in good to high yields with the trans-alkene isomer being favored. Typically less than 10% branched coupling products were observed (not shown). ... 

The Mizoroki-Heck reaction is a subtle and complex reaction which involves a great variety of intermediate palladium complexes. The four main steps proposed by Heck (oxidative addition, alkene insertion, )3-hydride elimination and reductive elimination) have been confirmed. However, they involved a considerable number of different Pd(0) and Pd(Il) intermediates whose structure and reactivity depend on the experimental conditions, namely the catalytic precursor (Pd(0) complexes, Pd(OAc)2, palladacycles), the Ugand (mono- or bis-phosphines, carbenes, bulky monophosphines), the additives (hahdes, acetates), the aryl derivatives (ArX, ArOTf), the alkenes (electron-rich versus electron-deficient ones), which may also be ligands for Pd(0) complexes, and at least the base, which can play a... 

Evidence for the intermediacy of a-arylpalladium acetate complexes c was provided by the isolation of their trinuclear dialkyl sulfide adducts [11]. The two following steps, insertion of the alkene 4 and )8-hydride elimination, correspond to the classical Mizoroki-Heck reaction pathway. The resulting palladium(0) species, which is likely to be stabilized in the form of a hydridopalladium carboxylate e, is then reoxidized by molecular oxygen to the initial palladium(II) acetate (a) under liberation of water. The precise mechanism of this reoxidation is not yet fully understood, but it seems that, at elevated oxygen pressures, it is not rate-determining even in the absence of promoters. Mechanistic studies by Jacobs and coworkers [10] indicate that the beneficial effect of adding transition metal salts, originally intended to facilitate this oxidation step, in fact arises from an acceleration... 

In their enantioselective total synthesis of the alkaloid cephalotaxine (246), Tietze and Schirok [127] used a combination of a Tsuji-Trost and a Mizoroki-Heck reaction (Scheme 8.62). It was necessary to adjust the reactivity of the two palladium-catalysed transformations to allow a controlled process. Reaction of 243a using Pd(PPh3)4 as catalyst led to 244, which furnished 245 in a second palladium-catalysed reaction. In this process, the nucleophilic substitution of the allylic acetate is faster than the oxidative addition of the arylbromide moiety in 243a however, if one uses the iodide 243b, then the yield drops dramatically due to an increased rate of the oxidative addition. 

A catalytic cycle arising from the common precatalyst mixture of Pd(OAc)2 and PPhs, termed the anionic pathway, has recently been proposed [ 14]. This pathway involves anionic palladinm(O) and palladium(II) intermediates in which the acetate anion is coordinated with palladinm in the catalytically active species persisting after oxidative addition. The anionic pathway has not been invoked or thoroughly explored for enantioselective intramolecular Mizoroki-Heck reactions. However, it may become more significant based on recent studies with Pd(OAc)2 and bidentate phosphine ligands for which the palladium(n) species is only formed in the presence of added acetate ion [15]. 

Amatore, C., Carre, E., Jutand, A. et al. (1995) Evidence for the ligation of palladium(O) complexes by acetate ions consequences on the mechanism of their oxidative addition with phenyl iodide and PhPd(OAc)(PPh3)2 as intermediate in the Heck reaction. Organometallics, 14, 5605-14. 

Prior to the discovery of the aryl-Heck reaction (Chapter 72), the direct Pd-promoted oxidative cyclization of diaryl amines to carbazoles was well known. In 1975 Akennark reported this reaction (Scheme 1, eqnation 1) [1], In addition, A -phenylanthranUic acid gave carbazole-l-carboxylic acid (60%). Miller and Moock used Pd(OAc)j to cyclize 6-anilino-5,8-dimethylisoquinoIine to eUipticine in low yield [2]. The second advance in this chemistry was reported independently by Bittner [3] and Furukawa [4], who described the Pd-mediated (stoichiometric) oxidative conversion of 2-anilino-l,4-benzoquinones and 2-anilino-l,4-naphthoquinones to the corresponding carbazole-l,4-diones and benzo[ ]carbazole-l,6-diones (equations 2, 3). Furukawa s studies included syntheses of several carbazolequinone alkaloids. In 1995 Akermark and colleagues developed catalytic versions (i.e., using tert-butyl hydrogen peroxide [TBHP] or oxygen) of this cyclization (equation 3) [5,6], which elevated the importance of this palladium oxidative cyclization, mainly because of the expense of Pd(OAc)2. Somewhat earlier, Knbiker used cupric acetate as a reoxidant in a synthesis of carbazole-l,4-quinones [7]. 

It was shown that palladacydes 1 [3c, 24] prepared from palladium] I) acetate and tris(o-tolyl)- or trimesitylphosphine are excellent catalysts for the Heck coupHng of triflates and halides including certain aryl chlorides. In some of these cases, a possible involvement of oxidation states +II and +IV in the catalytic cycle has been considered [25]. Similarly, other palladacydes such as 3 [26e,h] or 6 [27] have been used in the Heck reactions (Figure 8.1) [24, 26, 28]. It has been proposed that, at least for NC palladacydes, the reaction proceeds through the classical phosphine-free Pd(0)/Pd(II) catalytic cycle and that the active catalysts are actually slowly formed palladium clusters [29]. Besides classical palladacydes, complexes with pincer-type ligands such as 2 [30] have become very popular in palladium catalysis [31]. 

It should also be noted that various sources of palladium are given in the examples. The active oxidation state is Pd(0) in all these reactions, even when the source is Pd as in the Heck reaction example that uses palladium acetate. 

Palladium-catalyzed Direct Arylation of Indoles and Thiophenes. Five-membered ring heterocycles possessing only one heteroatom and no Af-oxide function can also be arylated using palladium(II) complexes, a phosphine ligand, and an inorganic base. In one example, a tandem palladium-catalyzed Heck coupling reaction and direct intramolecular C2 arylation reaction on a )V-(2-chlorobenzyl)-5-bromoindole was reported (eq 30). The procedure, which is catalyzed by palladium acetate, uses tn-tert-butylphosphonium tetrafluoroborate as a ligand and ferf-butyl acrylate as the alkene for the Heck reaction (eq 30). ... 

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