Reactions Mediated by Palladium

A reverse cross-coupling reactions mediated by palladium was used to develop a colorimetric sensitive chemodosimeter for the detection of trace palladium (II) salts [93]. The decolorization of 4 is produced by a nucleophilic attack of ethanethiol in basic DMSO solutions. Palladium detection is done via thiol scavenging from the 4-ethanethiol complex leading to a color turn-on of the parent squaraine. Naked-eye detection of Pd(NC>3)2 is as sensitive as 0.5 ppm in solution, and the instrument-based detection can go as low as 0.1 ppm. 

Both, hydration and hydroalkoxylation of olefins are usually carried out under acid catalysis or by oxymercuration reactions, although reactions mediated by palladium or by other metals have recently begun to emerge. In the latter case, nucleophilic addition of the O—H group is favored by a cationic palladium species that activates... 

Hillier AC, Grasa GA, Viciu MS, Lee HM, Yang CL, Nolan SP (2002) Catalytic cross-coupling reactions mediated by palladium/nucleophilic carbene systems. J Qrganomet Chem 653 69-82... 

Grasa, G. A., Viciu, M. S., Huang, J., Zhang, C., Trudell, M. L., Nolan, S. P. Suzuki-Miyaura Cross-Coupling Reactions Mediated by Palladium/lmidazolium Salt Systems. Organometallics 2002, 21,2866-2873. 

In addition to the success just described with the well-known named processes, a number of other macrocyclization reactions mediated by palladium complexes have been reported. The first of these approaches exploits the established chemistry of palladium Jt-allyl complexes for use in activation towards reaction with nucleophiles. This reaction was employed by Harran et al. as a critical step in the construction of a series of macrocycles such as 116 via 115) designed to significantly reduce the peptidic character of known active peptides (Scheme 11.14). " The approach tolerates a variety of functionality, including alcohols, amides, thioethers and selected heteroaromatics, and was also successfully conducted on solid support. 

Mixed triarylphosphines have been generated by addition-elimination reactions mediated by both palladium and nickel catalysts.45-47... 

Banfi L, Basso A, Cemlli V, Guanti G, Riva R (2008) Polyfunctionalized pyrrolidines by Ugi multicomponent reaction followed by palladium mediated Sfj2 cyclizations. J Org Chem 73 1608-1611... 

Others have investigated the kinetics of amination reactions mediated by catalyst systems employing the new electron-rich monodentate ligands. In particular, Hartwig has shown that for catalysis by a 1 1 palladium to Xn tert-butyl)phosphine system, a mechanism in which oxidative addition of aryl chlorides follows coordination of base to the palladium competes with the standard nonanionic pathway. Finally, Caddick, Cloke, and coworkers have studied amination reactions of aryl chlorides performed by palladium complexes of N-heterocyclic carbene ligands. They found the rate to be limited by the oxidative addition step, which occurs first through the dissociation of an NHC ligand. 

Huang, J., Nolan, S. P. Efficient Cross-Coupling of Aryl Chlorides with Aryl Grignard Reagents (Kumada Reaction) Mediated by a Palladium/lmidazolium Chloride System. J. Am. Chem. Soc. 1999, 121,9889-9890. 

Chapter 3 by Jie Jack Li presents a collection of very interesting total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. Five different types of palladium-mediated reactions are treated (I) oxidative cyclization reactions promoted by palladium (II) species (2) transmetallation reactions with organoboranes, organoslannanes, and organozinc reagents (3) inter- and intramolecular Heck reactions (4) reactions with it-allylpalladium as the intermediate and (5) reactions using C-N bond formation as the key step for the synthesis. 

Another type of oxycarborative addition is achieved when the organopalladium intermediate is trapped via alkene insertion. Thus, 1,5-hexadiene with acetic acid gives l-acetoxy-3-methylenecyclopentane (3) if mediated by palladium(ll) acetate10. This reaction is obviously restricted to 1,5-dienes, since other nonconjugated dienes and even some substituted 1,5-dienes lead to linear oxidation products. 

Few examples of carboaminations of normal double and triple bonds are known. Similarly to allylic alcohols, tosylated allylic amines with (cthoxy)ethene form 2-ethoxy-4-vinylpyrrolidines 2. The reaction, mediated by stoichiometric amounts of palladium(II) acetate, can be changed to catalytic if copper(II) acetate is added as reoxidant of palladium(O). Moderate stereoselectivity (d.r. 64 36) is reported, however, without further structural assignment. 

To this end, monodentate phosphine or bidentate PX (X=P, N, O) ligands have usually been employed as ancillary ligands for transition-metal-catalyzed reactions, with bulky tertiary alkyl phosphines proving particularly effective. Significant advances have been achieved in the use of less active aryl chlorides (bond strength C-Cl>C-Br>C-I) as chemical feedstock [5], with a number of processes mediated by palladium-bulky phosphine systems. This success is often explained by the effect of bulk and electron richness at the metal center along the catalytic cycle depicted in Fig. 1 [6]. 

As early as 1986, Kojima and colleagues reported on the carbonylative coupling of aryl iodides or benzyl halides with organoboranes in the presence of a catalytic amount of a palladium catalyst [9]. This was the first application of organoboranes in carbonylative coupling reactions mediated by 1.1 equivalent of Zn(acac)2 to favor the transmetallation. Various ketones have been produced in good yields starting from aryl iodides and benzyl chloride (Scheme 4.2). 

The oxidation of higher olefins has also been studied, and these reactions form ketones (Equation 16.102). Thus, the C-0 bond formation between water and the substituted olefin mediated by palladium occurs at flie internal carbon. For example, paUadium-catalyzed oxidation of propene forms acetone, and this reaction provides one industrial route to this material. Oxidations of substituted olefins to form ketones have also become a common method for the conversion of olefins to ketones during complex-molecule synthesis. Examples of the use of palladium-catalyzed oxidation in complex-molecule synthesis are described later in this chapter. 

Copper complexes have been used as reagents and as catalysts for the formation of carbon-carbon bonds. The most utilized reactions mediated by copper have been couplings of alkyl halides and sulfonates because copper complexes were unique for many years as reagents that would mediate the nucleophilic substitution of alkyl and aryl nucleophiles with alkyl halides. In recent years, work has been conducted to develop copper-catalyzed versions of cross couplings with aryl halides to address the issues of the cost of palladium catalysts. Although few examples of these processes currently rival those catalyzed by palladium complexes, they do illustrate the potential of copper complexes to catalyst these types of cross-coupling processes. 

Formation of Methyl Trifluoroacetate. In 1987, the conversion of methane to methyl trifluoroacetate mediated by palladium(II) acetate was reported, but the reaction was not catalytic at that time (eq. (16)) (31-33). 

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