Palladium catalyzed oxidations mechanism

SCHEME 137. Proposed mechanism for the palladium-catalyzed oxidation of terminal alkenes to methyl ketones using TBHP oxidant... 

Abstract Palladium-catalyzed oxidation reactions are among the most diverse methods available for the selective oxidation of organic molecules, and benzoquinone is one of the most widely used terminal oxidants for these reactions. Over the past decade, however, numerous reactions have been reported that utilize molecular oxygen as the sole oxidant. This chapter outlines the fundamental reactivity of benzoquinone and molecular oxygen with palladium(O) and their catalyst reoxidation mechanisms. The chemical similarities... 

Palladium-catalyzed oxidative allylic C-H functionalization provides attractive methods for the transformations of olefins, and their utility can be further enhanced by the development of more effective ways to use molecular oxygen (or air) to promote the catalytic cycle. The results outlined in this chapter summarize significant progress in the coupling reaction between terminal alkene and various types of nucleophiles. Further studies will be directed to explorations of the scope of nucleophilic reagents and olefins, and elucidation of the mechanisms of those reactions. Such studies will play an important role in the ongoing development of Pd-catalyzed C-H bond activations. 

Scheme 11.1 shows the reaction mechanism ofthe palladium-catalyzed oxidation of methyl acrylate to 3,3-dimethoxy methyl propionate. 

A palladium-catalyzed oxidative cyclization of tertiary enamines 7 to pyrroles 8 using copper acetate was reported by Guan and co-workers. Trifluo-roacetic acid as a stoichiometric additive was proven to be integral to the improvement of yield. The mechanism is proposed to go through electrophilic paUadation on the C—H of a tertiary enamine under acidic conditions which tri ers a cascade to form pyrroles 8. This method was used to synthesize a range of differentially functionalized 1,3,4-tri-substituted pyrroles (14OL3360). 

Scheme 8.31 Palladium-catalyzed oxidative carbonylative coupling of arylboronic acids with styrenes and proposed reaction mechanism...

Many types of palladium-catalyzed oxidative fimctionalizations of olefins related to the Wacker process have been developed, and these reactions are presented later in this chapter. To imderstand the relationship between these reactions and the basic Wacker oxidation of ethylene to form acetaldehye, the mechanism of the Wacker process is discussed before the related oxidation processes. 

Trifluoromethylated heteroarenes are widely applicable in the synthesis of pharmaceuticals. Using 10 mol% palladinm acetate as catalyst, TMSCF3 as trifluoro-methylating reagent, bidentate nitrogen-containing ligand L, and PhI(OAc)2 as oxidant, Liu and coworkers developed a novel palladium catalyzed oxidative trifluoromethylation of indoles at room temperatnre (Scheme 9.20). This reaction likely involves a palladium (II/IV) mechanism for the formation of the sp C—CF3 bond. 

The groups of Hu and You reported a remarkable palladium-catalyzed oxidative cross-coupling of Af-containing heteroarenes 62 with diversely substituted thiophenes 47 to afford products 63A-D (Scheme 10.19). The Af-containing heteroarenes included electron-rich heterocycles such as xanthines and azoles as weU as electron-poor heterocycles such as pyridine IV-oxides. In cases where heteroarenes demonstrated sluggish reactivity, CuBr was used as an additive to assist C—H bond activation. A computational study provided support for a two-fold C—H activation pathway via a CMD mechanism. 

Hull KL, Sanford MS (2009) Mechanism of benzoquinone-promoted palladium-catalyzed oxidative cross-coupling reactions. J Am Chem Soc 131 9651—9653... 

Palladium-catalyzed oxidative amination reactions are proposed to occur by the same basic mechanism as Waeker eyclizations (Scheme 12.11, Nu = NR). Stahl and co-workers developed a catalytic system for oxidative amination using pyridine as a ligand," but found some key challenges in this system, similar to the alcohol oxidation developed by Sigman and co-workers (i) pyridine, a kinetically labile ligand, could dissociate under the reaction... 

Amine activatitMi pathway has been well studied in catalysis by lanthanides, early transition metals, and alkali metals. In metal amide chemistry of late transition metals, there are mainly two pathways to synthesize metal amide complexes applicable under hydroamination conditions [54], One is oxidative addition of amines to produce a metal amide species bearing hydride (Scheme 8a). The other gives a metal amide species by deprotonation of an amine metal intermediate derived from the coordination of amines to metal center, and it often occurs as ammonium salt elimination by the second amine molecule (Scheme 8b). Although the latter type of amido metal species is rather limited in hydroamination by late transition metals, it is often proposed in the mechanism of palladium-catalyzed oxidative amination reaction, which terminates the catalytic cycle by p-hydride elimination [26]. Hydroamination through aminometallation with metal amide species demands at least two coordination sites on metal, one for amine coordination and another for C-C multiple bond coordination. Accordingly, there is a marked difference between the hydroamination via C-C multiple bond activation, which demands one coordination site on metal, and via amine activation. 

Recently, Y. Yamamoto reported a palladium-catalyzed hydroalkoxylation of methylene cyclopropanes (Scheme 6-25) [105]. Curiously, the catalysis proceeds under very specific conditions, i.e. only a 1 2 mixture of [Pd(PPh3)4] and P(o-tolyl)3 leads to an active system. Other combinations using Pd(0 or II) precursors with P(o-tolyl)3 or l,3-bis(diphenylphosphino)propane, the use of [Pd(PPh3)4] without P(o-tolyl)3 or with other phosphine ligands were all inefficient for the hydroalkoxylation. The authors assumed a mechanism in which oxidative addition of the alcohol to a Pd(0) center yields a hydrido(alkoxo) complex which is subsequently involved in hydropal-ladation of methylenecyclopropane. 

This reaction typifies the two possibilities of reaction routes for M-catalyzed addition of an S-X (or Se-X) bond to alkyne (a) oxidative addition of the S-X bond to M(0) to form 94, (b) insertion of alkyne into either the M-S or M-X bond to provide 95 or 96 (c) C-X or C-S bond-forming reductive elimination to give 97 (Scheme 7-21). Comparable reaction sequences are also discussed when the Chalk-Harrod mechanism is compared with the modified Chalk-Harrod mechanism in hydrosily-lations [1,3]. The palladium-catalyzed thioboratiori, that is, addition of an S-B bond to an alkyne was reported by Miyaura and Suzuki et al. to furnish the cis-adducts 98 with the sulfur bound to the internal carbon and the boron center to the terminal carbon (Eq. 7.61) [62]. 

In 1971, Brown and Davidson reported that 1,3-cyclohexadiene undergoes a palladium-catalyzed 1,4-diacetoxylation of unspecified stereochemistry28. The oxidant employed was p-benzoquinone. They were uncertain about the mechanism at the time but later work has shown that the reaction proceeds via a (jr-allyl)palladium intermediate and subsequent nucleophilic attack by acetate6,7. 

Palladium-catalyzed directed intramolecular activations of aryl C-H bonds have been reported, as in the phenyla-tion of heterocycle analogs. Palladacycles are proposed intermediates, acting as effective catalysts, and the mechanism is likely to proceed via oxidation of Pd(ll) to Pd(iv) by the iodonium salt, as for the Equation (57), which described the activation of benzylic i/-CH bonds (Equations (121)—(123).109... 

The mechanism of the Zn chloride-assisted, palladium-catalyzed reaction of allyl acetate (456) with carbonyl compounds (457) has been proposed [434]. The reaction involves electroreduction of a Pd(II) complex to a Pd(0) complex, oxidative addition of the allyl acetate to the Pd(0) complex, and Zn(II)/Pd(II) transmetallation leading to an allylzinc reagent, which would react with (457) to give homoallyl alcohols (458) and (459) (Scheme 157). Substituted -lactones are electrosynthesized by the Reformatsky reaction of ketones and ethyl a-bromobutyrate, using a sacrificial Zn anode in 35 92% yield [542]. The effect of cathode materials involving Zn, C, Pt, Ni, and so on, has been investigated for the electrochemical allylation of acetone [543]. 

The mechanism of palladium-catalyzed carbonylation of organic halides is generally assumed to involve oxidative additon of R-X to a Pd(0) species which is formed from the precursors on the action of CO + OH . Migratory insertion of R onto a coordinated CO followed by reaction with a nucleophile generates the product and gives back the catalytically active palladium(O) species (Scheme 5.4 A). 

A general simplified mechanism for palladium-catalyzed aerobic oxidation reactions and the different intermediates is given in Scheme 13. 

The opening step of the Buchwald-Hartwig reaction, similarly to the previous cases, is the oxidative addition of an aryl halide or sulfonate onto a low oxidation state metal. Although the term Buchwald-Hartwig reaction is usually reserved for palladium catalyzed processes, carbon-heteroatom bond formation also proceeds readily with nickel and copper. The nickel catalyzed processes follow a similar mechanism, while the distinctly different copper catalyzed reactions will be discussed in Chapter 2.5. 

---