Wacker-Type Oxidation Reactions

Wacker-type oxidative reactions of olefins with nucleophiles, reactions of zr-allyl-palladium complexes with nucleophiles, reactions based on chelation, and trans-metallation of organomercury compounds. 

Wacker-type oxidation reactions involving rearrangements. 

The Pd( 11)-catalyzed Wacker-type oxidation reaction is particularly useful to obtain prochiral ketones in aqueous reaction medium, which would enable a subsequent selective bioreduction process (Scheme 4.16) [66]. In one example, Schnapperelle... 

On the basis of the mechanism of Wacker-type oxidation reaction, what are the expected products if (a) but-l-ene is the substrate (b) but-2-ene is the substrate and (c) ethylene is oxidized in ROH rather than in water ... 

PdCOTfj CIPr) generated in situ from [Pd(p,-Cl)(Cl)(IPr)]j and AgOTf was reported to catalyse the copper-free Wacker-type oxidation of styrene derivatives using ferf-butyl hydroperoxide (TBHP) as the oxidant (Table 10.7) [41]. Reaction conditions minimised oxidative cleavage of styrene, which is a common side-reaction in Wacker-type oxidations. However, when franx-stilbene was used as a substrate, a significant amount of oxidative cleavage occurred. 

A survey of Wacker-type etherification reactions reveals many reports on the formation of five- and six-membered oxacycles using various internal oxygen nucleophiles. For example, phenols401,402 and aliphatic alcohols401,403-406 have been shown to be competent nucleophiles in Pd-catalyzed 6- TZ /fl-cyclization reactions that afford chromenes (Equation (109)) and dihydropyranones (Equation (110)). Also effective is the carbonyl oxygen or enol of a 1,3-diketone (Equation (111)).407 In this case, the initially formed exo-alkene is isomerized to a furan product. A similar 5-m -cyclization has been reported using an Ru(n) catalyst derived in situ from the oxidative addition of Ru3(CO)i2... 

In 1960, Moiseev and coworkers reported that benzoquinone (BQ) serves as an effective stoichiometric oxidant in the Pd-catalyzed acetoxylation of ethylene (Eq. 2) [19,20]. This result coincided with the independent development of the Wacker process (Eq. 1, Scheme 1) [Ij. Subsequently, BQ was found to be effective in a wide range of Pd-catalyzed oxidation reactions. Eor example, BQ was used to achieve Wacker-type oxidation of terminal alkenes to methyl ketones in aqueous DMF (Eq. 3 [21]), dehydrogenation of cyclohexanone (Eq. 4 [22]), and alcohol oxidation (Eq. 5 [23]). In the final example, 1,4-naphthoquinone (NQ) was used as the stoichiometric oxidant. 

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. 

The Pd-catalyzed conversion of terminal alkenes to methyl ketones is a reaction that has found widespread use in organic chemistry [87,88]. These reactions, as well as the industrial Wacker process, typically employ CuCh as a co-catalyst or a stoichiometric oxidant. Recently Cu-free reaction conditions were identified for the Wacker-type oxidation of styrenes using fBuOOH as the oxidant. An NHC-coordinated Pd complex, in-situ-generated (I Pr)Pd(OTf)2, served as the catalyst (Table 5) [101]. These conditions min-... 

Cu " Pd " -, Cu " -, and Pd -TSMs are completely different from each other in catalytic activity. Cu - and Pd " -TSMs catalyze no reaction and the total oxidation of propylene, respectively, whereas Cu Pd " -TSM catalyzes the oxidation to form acetone selectively, suggesting that the Wacker type oxidation takes place over the catalyst (41). The results are shown in Fig. 6. The higher initial activity is observed for Cu Pd -TSM with the lower Cu Pd ratio, namely the higher Pd " loading. This might be explainable by the second order dependency of the reaction rate on Pd " concentration, observed for the homogeneous system by Vargaftik et al. in the... 

It is surprising that the Wacker-type oxidation of 1-octene to 2-octanone is faster with the Co-salophen/zeolite catalyst than with the free complex. However, it is known that the Pd(II)-catalyzed oxidation of terminal olefins to ketones is accelerated by the presence of a catalytic amount of strong acid [1,2]. An explanation of the fester rate of the zeolite-encapsulated Co-salophen in this case is therefore that the acidic sites in the zeolite accelerate the reaction. 

With oxo synthesis, Wacker-type oxidations of alkenes is one of the older homogeneous transition-metal-catalyzed reactions [1], The most prominent example of this type of reaction is the manufacture of acetaldehyde from ethylene. This well-known reaction, which has been successfully developed on an industrial scale (Wacker process), combines the stoichiometric oxidation of ethylene by palladium ) in aqueous solution with the in situ reoxidation of palladium(O) by molecular oxygen in the presence of a copper salt (Eqs. 1 -4) [2]. 

The Wacker-type addition is the anti-addition of (most commonly) a heteroatom and a Pd(II) species across a C-C double bond. The Wacker-type oxidations are Pd(II)-catalyzed transformations involving heteroatom nucleophiles and alkenes or alkynes as electrophiles.27 In most of these reactions, the Pd(II) catalyst is converted to an inactive Pd(0) species in the final step of the process, and use of stoichiometric oxidants is required to effect catalytic turnover. For example, the synthesis of furan 33 from a-allyl-p-diketone 32 is achieved via treatment of the substrates with a catalytic amount of Pd(OAc)2 in the presence of a stoichiometric amount of CuCh-28 This transformation proceeds via Pd(II) activation of the alkene to afford 34, which undergoes nucleophilic attack of the enol oxygen onto the alkene double bond to provide alkylpalladium complex 35. p-Hydride elimination of 35 gives 36, which undergoes... 

Another Wacker-type oxidation is the oxidative cyclization reaction, which is the intramolecular union of two arenes with formal loss of H2 promoted by a Pd(II) species [typically Pd(OAc)2].33-36 In an early example of this transformation, treatment of diphenylamines 45 with Pd(OAc)2 in acetic acid yielded carbazoles 46.37 The role of acetic acid in such oxidative cyclization processes is to protonate one of the acetate ligands, which affords a more electrophilic cationic Pd(II) species, thereby promoting the initial electrophilic palladation of the aromatic ring. 

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... 

One of the exciting developments of the Wacker-type oxidation is the asymmetric synthesis of the reaction. For instance, using a new chiral bis(oxazoline) ligand L = 3,3 -Disubstituted 2,2 -bis(oxazolyl)-l,r-binaphthyls (boxax), a catalytic asymmetric Wacker -type cyclization converted allyl-phenol 55 to dihydrofuran 74 with 67% ee.ss... 

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). 

Cyclisation reactions involving a Wacker-type oxidative cyclisation have been reported to take place with very high enantioselectivity in some cases. ... 

The Wacker-type oxidation of the olefins is one of the oldest homogeneous transition metal-catalyzed reactions. The mechanism of the oxidation of ethylene to acetaldehyde by a PdCl2/CuCl2/02 system is shown in Figure 23. Interestingly, the selectivity of the oxidation of olefins with longer alkyl chains is dependent on their solubility in water. Furthermore, the production of chlorinated side-products and isomerized olefins has also occurred for olefins with low water solubility. In order to avoid the solubility issues, co-solvents such as DMSO, acetone, THF, dioxane, acetonitrile, DMF, and ethanol were used and DMF seemed to be the best. ... 

Wacker-type oxidations. Ethylene is oxidized to acetaldehyde in the presence of an aqueous solution of palladium (II) chloride and copper (II) chloride . The initial reaction is believed to follow a sequence of the type... 

To explain the observed behavior, it has been suggested [163,164,169,171] that the oxidation of terminal olefins to methyl ketones takes place via two complementary reactions occurring in a coupled mode (Scheme 12). These reactions are the activation of dioxygen (path A) and a Wacker type oxidation (path B). In path A, the cationic rhodium(II) complex 17, formed from RhCl, olefin, EtOH and... 

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