Palladium-catalyzed aerobic 1,4-oxidation

A palladium-catalyzed aerobic oxidative annulation of indoles, in the presence of ethyl nicotinate, has been disclosed.137,13711 The stereochemical outcome of this reaction indicates that an initial C-H functionalization at C(2) of the indole, followed by yvv/-carbopa 11 adation and ry -/ -H-elimination, operates (Equation (163)).137 This process has also been employed for the synthesis of benzofuran analogs.1373... 

Scheme 2 Simplified catalytic cycle for palladium-catalyzed aerobic oxidation ( oxidase ) reactions...

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

A remarkable number of palladium-catalyzed aerobic oxidation reactions of alcohols have been reported to date [15]. Unfortunately, although some progress has been made with heterogeneous Pd catalysts, such as Pd on activated carbon [16], Pd on pumice [17], Pd-hydrotalcite [18], Pd on Ti02 [19] and Pd/SBA-15 [20], most of these systems suffer from low catalytic activities and a limited substrate scope. 

Palladium-catalyzed aerobic oxidation of alcohols to aldehydes and ketones have been studied extensively in recent years, and a number of effective catalysts have been developed (Chart 2). This work has been the subject of several recent reviews [21,36-38,56,64-67] and will not be summarized in depth... 

In this context it is also worth mentioning that Showa Denko has developed a new process for the direct oxidation of ethene to acetic acid using a combination of palladium(II) and a heteropoly acid [104]. However, the reaction probably involves heteropoly acid-catalyzed hydration followed by palladium-catalyzed aerobic oxidation of ethanol to acetic acid rather than a classical Wacker mechanism. 

Much effort has been devoted to finding synthetically useful methods for the palladium-catalyzed aerobic oxidation of alcohols. For a detailed overview the reader is referred to several excellent reviews [163]. The first synthetically useful system was reported in 1998, when Peterson and Larock showed that simple Pd(OAc)2 in combination with NaHC03 as a base in DMSO as solvent catalyzed the aerobic oxidation of primary and secondary allylic and benzylic alcohols to the corresponding aldehydes and ketones, respectively, in fairly good yields [164, 165]. Recently, it was shown that replacing the non-green DMSO by an ionic liquid (imidazole-type) resulted in a three times higher activity of the Pd-catalyst [166]. 

Zeolite-encapsulated Fe-phthalocyanine and Co-salophen catalysts were used in the palladium-catalyzed aerobic oxidation of hydroquinone to benzoquinone, in the oxidation of 1-octene to 2-octanone and in the allylic oxidation of cyclohexene to 3-acetoxycyclohexene. These catalysts proved to be active in the above reactions and they were stable towards selfoxidation and it was possible to reuse them in subsequent runs. The specific activity of the encapsulated Fe-phthalocyanine catalyst was about four times higher than those of the free complex. 

Several metal macrocycles, like iron phthalocyanine and cobalt salophen were tested in these palladium-catalyzed aerobic oxidation of olefins and dienes. These tnacrocycles were able to activate the molecular oxygen, but in the homogeneous system several problems have arised, such as poor solubility, self-degradation and the difficulty to reuse theses complexes. A... 

Figure 11.3 outlines our three-step route from acrolein to 1,3-propanediol based on the palladium-catalyzed aerobic oxidation as presented in Section 11.2.2. 

New advances in palladium-catalyzed aerobic oxidations (N-heterocycles... 

Evano and colleagues disclosed a modular indole synthesis via the intramolecular carbocupration of N-aryl-ynamides (124 125) (130L3122).A series of indole derivatives was prepared by Jiao via the palladium-catalyzed aerobic oxidative intramolecular hydroamination and C-H functionalization of N-alkynylanilines (13T4408). Suh reported a microwave-assisted synthesis of 3-functionalized indoles via an intramolecular arene-alkene coupling of o-iodoanilino enamines (13T7211). 

TABLE 2 Palladium-Catalyzed Aerobic Oxidation of Alcohols. 

Limited studies are focused on the coupling of primary and secondary phosphines with aryl electrophiles due to palladium-catalyzed aerobic oxidation of R PH to R PCO) [225], Palladium-catalyzed cross-coupling of primary or secondary phosphines has been reported with aryl iodides (Scheme 20.67) [226,227], Buchwald and coworkers utilized Pd(OAc)j-DTPF for the coupling of secondary aryl phosphines with aryl halides [256]. This system is also effective for the reaction of phosphines with aryl chlorides. 

Palladium(II) is also capable of mediating the oxidation of alcohols via the hydridometal pathway shown in Figure 1. Blackburn and Schwarz first reported the Pd(OAc)2-NaOAc-catalyzed aerobic oxidation of alcohols in 1977. However, activities were very low, with turnover frequencies of the order of 1 h . Subsequently, much effort has been devoted to finding synthetically useful methods for the palladium-catalyzed aerobic oxidation of alcohols. For example, the giant palladium cluster, Pds6iphen6o(OAc)tgo , was shown to catalyze the aerobic oxidation of primary allylic alcohols to the corresponding a,0-unsaturated aldehydes (Reaction 14) . 

The paUadium(II) -catalyzed aerobic oxidation of alcohols is well documented. A general problem encountered in palladium-catalyzed aerobic oxidations is the sluggish reoxidation of Pd(0) to Pd(II), which results in the agglomeration of the Pd(0) particles to palladium black and accompanying deactivation of the catalyst. In the classical Wacker process for the oxidation of ethylene to acetaldehyde in an aqueous medium, this problem is circumvented... 

Figure 7.13 Palladium-catalyzed aerobic oxidation of terminal olefins in water.

Caspi, D., Ebner, D., Bagdanoff, J., et al. (2004). The Resolution of Important Pharmaceutical Building Blocks by Palladium-Catalyzed Aerobic Oxidation of Secondary Alcohols, A fv. Syrah. Catal., 346, pp. 185-189. 

Vlaar, T., Cioc, R. C., Mampuys, R, Maes, B. U. W., Orru, R. V. A., Ruijter, E. (2012). Sustainable synthesis of diverse privileged heterocycles by palladium-catalyzed aerobic oxidative isocyanide insertion. Angewandte Chemie International Edition, 51, 13058-13061. 

Gowrisankar S, Neumann H, Gordes D, Thurow K, Jiao H, Beller M. A convenient and selective palladium-catalyzed aerobic oxidation of alcohok. Chem Eur J. 2013 19 15979-15984. 

Caspi DD, Ebner DC, Bagdanoff JT, Stoltz BM. The resolution of important pharmaceutical building blocks by palladium-catalyzed aerobic oxidation of secondary alcohols. Adv. Synth. Catal. 2004 346 185-189. 

Schultz MJ, Adler RS, Zitakiewicz W, Privalov T, Sigman MS (2005) Using mechanistic and computational studies to explain ligand effects in the palladium-catalyzed aerobic oxidation of alcohols. J Am Chem Soc 127 8499-8507... 

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