Palladium catalysts Wacker-type

Palladium-catalyzed, Wacker-type oxidative cycHzation of alkenes represents an attractive strategy for the synthesis of heterocycles [139]. Early examples of these reactions typically employed stoichiometric Pd and, later, cocat-alytic palladium/copper [140-142]. In the late 1970s, Hegedus and coworkers demonstrated that Pd-catalyzed methods could be used to prepare nitrogen heterocyles from unprotected 2-allylanilines and tosyl-protected amino olefins with BQ as the terminal oxidant (Eqs. 23-24) [143,144]. Concurrently, Hosokawa and Murahashi reported that the cyclization of allylphenol substrates can be accomplished by using a palladium catalyst with dioxygen as the sole stoichiometric reoxidant (Eq. 25) [145]. 

The field of homogeneous palladium catalysis traces its origin to the development of the Wacker process in the late 1950s (Eq. 7) [83]. Since this discovery, palladium-catalyzed reactions have evolved into some of the most versatile reactions for the synthesis of organic molecules [84,85]. Palladium-catalyzed Wacker-type oxidation of alkenes continues to be an active field of research [86-88], and several recent applications of NHC-coordinated Pd catalysts have been reported for such reactions. 

Heterogeneous catalysts such as Ru-Al-Mg-hydrotaldte, Ru-Co-Al-hydrotalcite, Ru-hydroxyapatite (RuHAP) (Eq. (7.40)) [91], RU-AI2O3 [92a,b], and Ru/A10(OH) [92c] are highly efficient catalysts for aerobic oxidation of alcohols. In these oxidation reactions, the key step is postulated as the reaction of Ru-H with O2 to form Ru-OO H, in analogy to Pd-OOH, which has been shown to operate in the palladium-catalyzed Wacker-type asymmetric oxidation reaction [93]. It is noteworthy that ruthenium on carbon is simple and efficient for the oxidation of alcohols (Eq. (7.41)) [92d]. 

Wacker cyclization has proved to be one of the most versatile methods for functionalization of olefins.58,59 However, asymmetric oxidative reaction with palladium(II) species has received only scant attention. Using chiral ligand 1,1 -binaphthyl-2,2 -bis(oxazoline)-coordinated Pd(II) as the catalyst, high enantioselectivity (up to 97% ee) has been attained in the Wacker-type cyclization of o-alkylphenols (66a-f) (Scheme 8-24). 

The reaction is highly exothermic as one might expect for an oxidation reaction. The mechanism is shown in Figure 15.1. Palladium chloride is the catalyst, which occurs as the tetrachloropalladate in solution, the resting state of the catalyst. Two chloride ions are replaced by water and ethene. Then the key-step occurs, the attack of a second water molecule (or hydroxide) to the ethene molecule activated towards a nucleophilic attack by co-ordination to the electrophilic palladium ion. The nucleophilic attack of a nucleophile on an alkene coordinated to palladium is typical of Wacker type reactions. 

A development of the last two decades is the use of Wacker activation for intramolecular attack of nucleophiles to alkenes in the synthesis of organic molecules [9], In most examples, the nucleophilic attack is intramolecular, as the rates of intermolecular reactions are very low. The reaction has been applied in a large variety of organic syntheses and is usually referred to as Wacker (type) activation of alkene (or alkynes). If oxygen is the nucleophile, it is called oxypalladation [10], Figure 15.4 shows an example. During these reactions the palladium catalyst is often also a good isomerisation catalyst, which leads to the formation of several isomers. 

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... 

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). 

The oxidative carbonylation of arenes to aromatic acids is a useful reaction which can be performed in the presence of Wacker-type palladium catalysts (equation 176). The stoichiometric reaction of Pd(OAc)2 with various aromatic compounds such as benzene, toluene or anisole at 100 °C in the presence of CO gives aromatic acids in low to fair yields.446 This reaction is thought to proceed via CO insertion between a palladium-carbon (arene) allyl chloride, but substantial amounts of phenol and coupling by-products are formed.447... 

The catalytic oxycarbonylation of benzene and naphthalene to benzoic or naphthoic acid in the presence of Wacker-type catalysts has been reported in several patents,376,448 but difficulties in reoxidizing the reduced palladium have inhibited industrial use of this chemistry. 

The reaction media for Wacker-type reactions are highly corrosive. This is due to the presence of free acids (acetic acid for vinyl acetate), ions like Cl, and dioxygen. For any successful technology development, the material of construction for the reactors is a major point of concern (see Section 3.1.4). Some progress in this respect has recently been made by the incorporation of heteropolyions such as [PV14042]9 in the catalytic system. The heteropolyions probably act as redox catalysts. A seminonaqueous system is used for this modified catalytic system, and the use of low pH for dissolving copper and palladium salts is avoided. 

The catalytic system for this entire class of reactions is quite similar, being a Wacker type catalyst, such as a palladium salt, in the presence of a cooxidant (for instance CuClj). 

Substituted furo[2,3-fc]pyridones were assembled by a Pd-mediated sequential crosscoupling Sonogashira reaction-Wacker-type heteroannulation and deprotection reactions of pyridones, aUcynes and organic halides in an one-pot operation <03OL2441>. The coupling products of pyridones and alkynes could be separated and a single palladium catalyst intervened in three different transformations. 

Quite a surprising reaction has recently been reported [74]. With a catalyst of palladium metal on carbon in aqueous phase, propene is oxidized with oxygen to give acrylic acid, probably via allyl alcohol in a allylic-type oxidation (for allylic oxidation see Section 3.3.14). In the presence of chloride or oxidants the normal Wacker-type reaction product acetone arises. 

In 2003, Stoltz at CalTech described a palladium-catalyzed oxidative Wacker cyclization of o-allylphenols such as 55 in nonpolar organic solvents with molecular oxygen to afford dihydrobenzofurans such as 56.44 Interestingly, when (-)-sparteine was used in place of pyridine, dihydrobenzofuran 56 was produced asymmetrically. The ee reached 90% when Ca(OH)2 was added as an additive. Stoltz considered it a stepping stone to asymmetric aerobic cyclizations. In 2004, Mufiiz carried out aerobic, intramolecular Wacker-type cyclization reactions similar to 55—>56 using palladium-carbene catalysts.45 Hiyashi et al. investigated the stereochemistry at the oxypalladation step in the Wacker-type oxidative cyclization of an o-allylphenol. Like o-allylphenol, o-allylbenzoic acid 57 underwent the Wacker-type oxidative cyclization to afford lactone 58.47... 

Palladium catalysts are widely used in liquid phase aerobic oxidations, and numerous examples have been employed for large-scale chemical production (Scheme 8.1). Several industrially important examples are the focus ofdedicated chapters in this book Wacker and Wacker-type oxidation of alkenes into aldehydes, ketones, and acetals (Scheme 8.1a Chapters 9 and 11), 1,4-diacetoxylation of 1,3-butadiene (Scheme 8.1b Chapter 10), and oxidative esterification of methacrolein to methyl methacrylate (Scheme 8.1c Chapter 13). In this introductory chapter, we survey a number of other Pd-catalyzed oxidation reactions that have industrial significance, including acetoxylation of ethylene to vinyl acetate (Scheme 8. Id), oxidative carbonylation of alcohols to dialkyl oxalates and carbonates (Scheme 8.1e), and oxidative coupling of dimethyl phthalate to 3,3, 4,4 -tetramethyl biphenylcarboxy-late (Scheme 8.1f). 

Two types of reactions are summarized in this section (i) the intermolecular carbopalladation leads to a Pd functionality such as alkyl-, alkenyl-, or allylpalladium complexes, which is intramolecularly trapped by a heteroatom (again Wacker-type processes are mechanistic alternatives) (ii) the palladium catalyst is not directly involved in the hetero-cyclization step, but the carbopalladation builds up a suitable functionality or changes bond angles so that the heterocyclization can take place. 

Allylpalladium complexes with BOX-type ligands and glucopyrano-oxazoline-palladium catalysts were used as catalysts for enantioselective allylic substitution (277). A chiral bisoxazoline ligand (BOXBZ) developed by Pfaltz has been used for asymmetric carbo- and heteroannulation reactions (278). An axial binaphthyl-based ligand possessing oxazolyl substituents (BOXAX) was developed by Hayashi and co-workers and successfully applied for the asymmetric Wacker-type cyclization (279). 

Buchwald described an oxypalladation reaction, followed by a C-H functionalization. This entirely intramolecular reaction is initiated through a 5-exo Wacker-type cychzation of 84. The resulting a-alkyl-paUadium intermediate M provides subsequent C-H activation at the neighboring arene, which allows a paUadium(II) intermediate N bearing a-alkyl and o-aryl substituents, respectively. Reductive elimination provides the C-C bond installation of 85 with the concomitant release of a paUadium(O) catalyst state. Reoxidation imder aerobic conditions, most probably through a palladium(II) -peroxo complex and protonolysis with the acetic add hber-ated in the previous steps, regenerates the original paUadium(II) diacetate catalyst. 

Other than the palladium-alkyl nitrite system, the usual Wacker-type catalyst, which utihzes molecular oxygen as stoichiometric oxidant, is commonly employed.It has superior catalyst efhciency but shows lower productivity than that of the nitrite system. 

---