Palladium-catalyzed Allylic Oxidations

In the well-known Wacker process ethylene is converted to acetaldehyde by aerobic oxidation in an aqueous medium in the presence of PdCl2 as catalyst and CuCl2 as cocatalyst [7], Terminal olefins afford the corresponding methyl ketones. Oxidative acetoxylation of olefins with Pd(II) salts as catalysts in acetic acid was first reported by Moiseev and coworkers [8], The addition of an alkali metal acetate, e. g. NaOAc, was necessary for the reaction to proceed. Palladium black was also found to be an active catalyst under mild conditions (40-70 °C, 1 bar) in the liquid phase, if NaOAc was added to the solution before reducing Pd(II) to Pd black, but not afterwards [9,10]. These results suggested that catalytic activity 

These pioneering studies formed the basis for the development of commercial processes for the production of allyl acetate by oxidative acetoxylation of propylene (Eq. 1). Processes are operated by Showa Denko and Daicel in Japan and Hoechst and Bayer in Europe [2,11], The reaction is usually performed in the gas phase, e. g. at 140-170 °C over Pd(OAc)2/Cu(OAc)2/KOAc/Si02 or Pd/ KOAC/S1O2 catalysts and allyl acetate is formed with 95 % selectivity. Allyl acetate is the raw material for the production of epichlorohydrin and glycerol. 

Lyons [4] showed that aerobic oxidation of propylene in acetic acid containing NaOAc, over a Pd/C catalyst at 65 °C, afforded allyl acetate with 99 % selectivity. To obtain high reaction rates it was necessary to pretreat the palladium cat- 

Moiseev and coworkers showed [10,13] that giant palladium clusters with an idealized formula Pd56iL5o(OAc)igo (L = phenanthroline or bipyridine) are highly active catalysts for allylic oxidation of olefins. The catalytically active solution was prepared by reduction of Pd(OAc)2, e. g. with H2, in the presence of the ligand, L, followed by oxidation with O2. The giant palladium cluster catalyzed the oxidation of propylene to allyl acetate under mild conditions. Even in 10% aqueous acetic acid, allyl acetate selectivity was 95-98 % [10]. Oxidation catalyzed by Pd-561 in water afforded a mixture of allylic alcohol (14%), acrolein (2%), and acrylic acid (60%), and only 5% acetone [10]. 

Analogous allylic oxidations of higher olefins over heterogeneous palladium catalysts afford mixtures of products owing to the unsymmetrical nature of the f-allyl intermediate. For example, cis- or trans-2-butene gives a mixture of branched and linear allylic acetates. With olefins containing more than four carbon atoms palladium-catalyzed isomerization can lead to complex mixtures of products, which severely restricts the synthetic scope of these reactions. 

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Palladium-catalyzed allylic oxidations, in contrast, are synthetically useful reactions. Palladium compounds are known to give rise to carbonyl compounds or products of vinylic oxidation via nucleophilic attack on a palladium alkene complex followed by p-hydride elimination (Scheme 9.16, path a see also Section 9.2.4). Allylic oxidation, however, can be expected if C—H bond cleavage precedes nucleophilic attack 694 A poorly coordinating weak base, for instance, may remove a proton, allowing the formation of a palladium rr-allyl complex intermediate (89, path by694-696 Under such conditions, oxidative allylic substitution can compete... 

H. Greenberg and J. E. Backvall, in Transition Metals for Organic Synthesis, Vol. 2, M. Beller and C. Bolm, Eds., Wiley-VCH, Weinheim, 1998, 200-212. Palladium-Catalyzed Allylic Oxidation. 

Figure lA. Palladium-catalyzed allylic oxidation of an alkene. 

The Tsuji-Trost reaction is the palladium-catalyzed allylation of nucleophiles [110-113]. In an application to the formation of an A-glycosidic bond, the reaction of 2,3-unsaturated hexopyranoside 97 and imidazole afforded A-glycopyranoside 99 regiospecifically at the anomeric center with retention of configuration [114], Therefore, the oxidative addition of allylic substrate 97 to Pd(0) forms the rc-allyl complex 98 with inversion of configuration, then nucleophilic attack by imidazole proceeds with a second inversion of configuration to give 99. 

A. 1.1. Covalently Functionalized Dendrimers Applied in a CFMR The palladium-catalyzed allylic substitution reaction has been investigated extensively in the preceding decades and provides an important tool for the formation of carbon—carbon and carbon—heteroatom bonds 14). The product is formed after attack of a nucleophile to an (f/ -allyl)Pd(II) species, formed by oxidative addition of the unsaturated substrate to palladium(0) (Scheme 1). To date several nucleophiles have been used, mostly resulting in the formation of carbon—carbon and... 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

A palladium-catalyzed allylic sulfonate-sulfone rearrangement with chiral sulfonates produced 92% optical yields (equation 3S9).448 449 Presumably, the optically active sulfonate induces chirality in the oxidative addition by Pd° in these reactions. 

In the group of Backvall a method was developed involving palladium and benzoquinone as cocatalyst (Fig. 4.42) [103]. The difficulty of the catalytic reaction lies in the problematic reoxidation of Pd(0) which cannot be achieved by dioxygen directly (see also Wacker process). To overcome this a number of electron mediators have been developed, such as benzoquinone in combination with metal macrocycles, heteropolyacids or other metal salts (see Fig. 4.42). Alternatively a bimetallic palladium(II) air oxidation system, involving bridging phosphines, can be used which does not require additional mediators [115]. This approach would also allow the development of asymmetric Pd-catalyzed allylic oxidation. 

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]. 

Three research groups discovered almost at the same time that non-C2-symmetrical oxazolines of the type 32 can be even more effective ligands for asymmetric catalysis than type 4 ligands (Fig. 11). For the palladium-catalyzed allylic substitutions on 62, record selectivities could be reached using 32 (X = PPhj) [30]. It seems that not only steric but also electronic factors, which cause different donor/acceptor qualities at the coordination centers of the ligand, seem to play a role here [31]. The reaction products can subsequently be converted to interesting molecules, for example 63 (Nu = N-phthalyl) can be oxidized to the amino acid ester 64 [32]. 

In the oxidation of 2-octenyl acetate, in addition to the normal oxidation, palladium-catalyzed allylic rearrangement and subsequent oxidation took place to give a small amount of 3-acetoxy-2-octanone as a byproduct. Ethers of secondary allylic alcohols also underwent the regioselective oxidation to give the corresponding 3-alkoxy ketones in 30-40% yields. But in this case too, by-products derived from the allylic reanangement a subsequent oxidation were also detected. Results of the oxidation of some allyl ethers are shown in Table 3. °... 

In order to permit complete conversion to one product enantiomer under the influence of a chiral catalyst, substrates for palladium-catalyzed allylic substitution either have to possess a meso structure (equation 1) or else give rise to complexes with 7t-allyl ligands as depicted in equations 2 and 3. Whereas oxidative addition of the substrate to the palladium(O) species constitutes the enantioselective step for meso compounds (equation 1), nucleophilic attack determines the absolute configuration of the product for reactive intermediates with a meso tt-allyl ligand (equation 2) or a zr-allyl unit that undergoes rapid epimerization by the n-a-n mechanism10-59 relative to substitution (equation 3). 

The stereoselective allylation of aldehydes was reported to proceed with allyltrifluorosilanes in the presence of (S)-proline. The reaction involves pentacoordinate silicate intermediates. Optical yields up to 30% are achieved in the copper-catalyzed ally lie ace-toxylation of cyclohexene with (S)-proline as a chiral ligand. The intramolecular asymmetric palladium-catalyzed allylation of aldehydes, including allylating functionality in the molecules, via chiral enamines prepared from (5)-proline esters has been reported (eq 15). The most promising result was reached with the (S)-proline allyl ester derivative (36). Upon treatment with Tetrakis(triphenylphosphine)palladium(0) and PPh3 in THF, the chiral enamine (36) undergoes an intramolecular allylation to afford an a-allyl hemiacetal (37). After an oxidation step the optically active lactones (38) with up to 84% ee were isolated in high chemical yields. The same authors have also reported sucessful palladium-catalyzed asymmetric allylations of chiral allylic (S)-proline ester enamines" and amides with enantiomeric excesses up to 100%. 

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. 

Another advantage of dendrimer-based catalysts concerns their easy recovery by stabilization at the surface of a polymer. The principal activities in dendritic catalysis lie in homogeneous catalysis, including Kharash addition of CC14 to methacrylate, palladium-catalyzed allylic alkylation, hydrogenation of olefins, hydroformylation, cyclopropanation, and oxidation.258 Dendrimers with redox-active cores have been proposed as promising materials for miniaturized information-storage circuits.259... 

The generally accepted mechanism of palladium-catalyzed allylic substitutions is shown in Scheme 1. An allylic substrate 1, typically an acetate or a carbonate, reacts with the catalyst, which enters the catalytic cycle at the Pd(0) oxidation level. Both Pd(0) and Pd(II) complexes can be used as precatalysts, because Pd(II) is easily reduced in situ to the active Pd(0) form. Presumably, the reaction is initiated by formation of a Ji-complex which eliminates X to produce an (ri -allyl)palladium(II) complex. The product of this oxidative addition can... 

Keywords Palladium-catalyzed Allylic C-H bond activation Unactivated olefin 7t-allylpalladium Oxidative functionalization... 

Since the first example of catalytic reaction of palladium-catalyzed allylic acetoxylation was reported by Haszeldine and coworkers in 1966 [10], cyclohexene has been a benchmark substrate for this kind of reactions under different oxidative conditions, which are well documented in reviews and books [11, 12]. The proposed mechanism for allylic acetoxylation of cyclohexene is illustrated in... 

Palladium-catalyzed allylic acetoxylation has also been applied to terpene substrates [17], e. g. (/ )-limonene (Eq. 2), albeit using stoichiometric amounts of Cu(II) or benzoquinone as the oxidant. 

Jiang s group developed a palladium-catalyzed direct oxidative carbonylation of allylic C-H bonds with carbon monoxide [73]. This observation provides a novel route for accessing / -enoic acid esters with high regioselectivity (Scheme 8.13). Preliminary results from deuterium-labeling experiments indicated that the aUyhc C-H activation process is an irreversible rate-determining step. 

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