Acetoxylation palladium catalyzed

Pd-hydroquinone-mediated electrochemical 1,4-diacetoxylation of cyclohexa-1,3-diene (118), leading to 1,4-diacetoxycyclo-hex-2-ene (119), has been investigated (Scheme 46) [156]. Palladium-catalyzed indirect electrochemical monoacetoxylation of olefins has been attained in an MeCN/Ac0H-NaC104/Ac0Na/Pd(0Ac)2-Cu(OAc)2-(C) system. The acetoxylation of cyclohexene produces unsaturated esters with less current efficiency, giving a 1 1 mixture of allylic and vinylic products [118]. 

Palladium-catalyzed addition of oxygen nucleophiles to alkenes dates back to the Wacker process and acetoxylation of ethylene (Sects. 1 and 2). In contrast, catalytic methods for intermolecular oxidative amination of alkenes (i.e., aza-Wacker reactions) have been identified only recently. Both O2 and BQ have been used as oxidants in these reactions. 

Scheme 14 Possible outcomes for the palladium-catalyzed oxidative acetoxylation of alkenes...

The homogeneous palladium-catalyzed process for acetoxylation was never commercialized because of low selectivity and the difficulty in separating the catalyst from the reaction mixture. Heterogeneous palladium catalysts applied in the gas phase, in turn, quickly lose activity caused by buildup of polybutadiene. The Mitsubishi process uses a Pd-Te-on-active-carbon catalyst in the liquid phase. Tellurium apparently prevents palladium elution to acetic acid. 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

First discovered by Moiseev et a/.,416 the palladium-catalyzed acetoxylation of ethylene to vinyl acetate has been the subject of very active investigations, particularly in industry, as shown by the considerable number of patents existing in this area. Vinyl acetate is an extremely important petrochemical product which is used for the synthesis of polymers such as poly(vinyl acetate) and poly(vinyl alcohol). Most of its annual production ( 2.6 Mt) results from the acetoxylation of ethylene (equation 160). 

When palladium-catalyzed acetoxylation is carried out in the presence of nitrate or nitrite ions, ethylene glycol monoacetate (EGMA) results as the major product of the reaction (equation 163).420... 

Arpe and Hornig595 carried out a thorough investigation of palladium-catalyzed acetoxylation of benzene in acetic acid. Selectivities as high as 78% were observed with a heterogeneous Pd/Au-on-Si02 catalyst at 155°C. 

Figure 28 shows that the chemistry involved in the Wacker process could in principle be extended to other nucleophiles. The modern catalytic manufacturing process making vinyl acetate from ethylene and acetic acid is based on the observation that palladium catalyzed oxidation of ethylene to acetaldehyde can be converted into an acetoxylation reaction if carried out in a solution of acetic acid and in the presence of sodium acetate (Equation 42). 

FUNCTIONALIZATION OF 1,3-OIENES VIA PALLADIUM-CATALYZED CHLORO-ACETOXYLATION AND ALLYLIC AMINATION l-ACETOXY-4-DIETHYLAMIN0-2-BUTENE AND 1-ACET0XY-4-BENZYLAMIN0-2-BUTENE... 

Acetoxylations and Other Palladium-Promoted or Palladium-Catalyzed Reactions... 

Since the first example of catalytic reaction of palladium-catalyzed allylic acetoxylation was reported by Haszeldine and coworkers in 1966 [10], cyclohexene has been a benchmark substrate for this kind of reactions under different oxidative conditions, which are well documented in reviews and books [11, 12]. The proposed mechanism for allylic acetoxylation of cyclohexene is illustrated in... 

Palladium-catalyzed allylic acetoxylation has also been applied to terpene substrates [17], e. g. (/ )-limonene (Eq. 2), albeit using stoichiometric amounts of Cu(II) or benzoquinone as the oxidant. 

Palladium-catalyzed aUyUc C-H acetoxylation (acyloxylation) of alkenes is one of the synthetically most established C-H functionabzation methods [57-62]. These reactions are conducted under oxidative reaction conditions. In the most commonly used approach, the reaction proceeds via a Pd(II)/Pd(0) catalytic cycle and benzoquinone (BQ) is used for reoxidation of Pd(0) and activation of the nudeophihc (acetate) attack [61, 62],... 

Despite the recent progress in palladium-catalyzed diastereoselective iodin-ation, acetoxylation, and arylation reactions,Pd-catalyzed enantioselective C—H bond functionalizations are rather challenging due to lack... 

Yu and Movassaghi developed the palladium-catalyzed meta-C-H olefi-nation (257,43 examples,43-96% yield),arylation (258,8 examples,43-63% yield), and acetoxylation (259,4 examples, 26-74% yield) of indolines using a directing group with a U-shaped template (256).This constitutes the first... 

The stereogenic centers were then introduced by palladium-catalyzed dynamic kinetic asymmetric transformatitHi. ITierefore, 41 was coupled with lactone 42 in the presence of chiral ligand (RJt)-43 and gave 44 in 89% yield. The synthesis of 42 is shown below in Scheme 2.6. Compound 44 was subjected to an intramolecular Heck reaction followed by acidic cleavage of the ester function 45). The intramolecular Heck reaction only produced one diastereomer, because the c/s-annelated rings are favored. Scandium(lll)-mediated cyclizatitMi and reduction of the lactone with DIB ALII yielded (-)-aflatoxin Baa (46). It was acetoxylated and then pyiolyzed to give (-)-aflatoxin Bi (1) in 1.6% overall yield and nine linear steps from catechol (40). 

Palladium-catalyzed aromatic C-H acetoxylation was first reported in 1966 [100, 101]. In 1971, Henry proposed Pd(IV) intermediates in the Pd-catalyzed acetoxylation of benzene with K2Cr207 in AcOH [102], Subsequent reports by Stock [103] and Crabtree [104] also discussed the possible intermediacy of Pd(IV) complexes in the acetoxylation of benzene (Fig. 27a). In 2004, Sanford reported the regioselec-tive ort/to-acetoxylation of 2-arylpyridines and proposed a reaction mechanism involving aromatic C-H metallation at Pd(II), oxidation of the resulting aryl Pd(II) intermediate to a Pd(IV) complex, and product-forming C-O reductive elimination (Fig. 27b) [105-108]. 

A particularly significant and useful contribution of transition metals in fine organic synthesis as well at the industrial level is based on their use as catalysts. This aspect is of course particularly important with expensive transition metals (Rh, Os, Pd, etc.). Indeed, there are numerous examples of selective processes which have never been developed up to the industrial stage because of catalyst costs, especially when some (even minor) loss of the catalyst could not be avoided. This was, for example, the case for palladium-catalyzed benzylic acetoxylation reactions, and several rhodium-catalyzed reactions, such as the direct ethylene glycol production from syngas (prohibitive pressures being an additional major drawback in this latter case). 

This one-step transformation of an alkene to an allylic acetate compares well with other methods of preparation such as hydride reduction of a, 8-unsaturated carbonyl compounds followed by esterification. The scope and limitations of the reaction have been investigated. The allylic acetoxylation proceeds via a TT-allylpalladium intermediate, and as a result, substituted and linear alkenes generally give several isomeric allylic acetates. With oxygen nucleophiles the reaction is quite general, and reactants and products are stable towards the reaction conditions. This is normally not yet the case with nitrogen nucleophiles, although one intramolecular palladium-catalyzed allylic amination mechanistically related to allylic acetoxylation has been reported. ... 

In 2012, Chen and coworkers developed the palladium-catalyzed intramolecular amination of C(sp )-H at y and 5 positions to synthesize a series of nitrogen-containing heterocycles [15], including azetidine (Scheme 2.11), pyrrolidines, and indolines. With the optimal conditions, using catalytic Pd(OAc)2, an oxidant (PhI(OAC)2, 2.5 equiv.) and an acid additive (AcOH) in toluene at llO C, Chen tested them on other picolinamide substrates bearing primary y-C(sp )-H bonds surprisingly, the seemingly unfavorable four-membered azetidine was obtained as the major product. It is possible that a Pd(IV) intermediate was formed via PhI(OAC)2 oxidation of the palladacycle intermediate because the subsequent C-N and C-O reductive elimination pathways would lead to the formation of the cyclized and acetoxylated product. It was also noteworthy that no P H elimination product was detected under the aforementioned reaction conditions. 

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