Palladium complexes fluorous

Palladium-catalyzed cross-coupling reactions often require relatively large amounts of catalysts which have to be removed from the reaction product. Fluorous palladium complexes offer a solution to this problem, since they are soluble in fluorous solvents and can be readily separated from the organic product by liquid-liquid extractions. 

Most of the reported work on Mizoroki-Heck reactions in fluorous media applies palladium salts and free ligands. There are only five reports on the usage of preformed fluorous palladium complexes (Table 15.1, entries 1 ) [64-68]. They all used a biphasic system with an organic solvent and a fluorous catalyst that dissolved only at elevated temperatures. Gladysz and coworkers [64, 65] recovered the catalyst 22 in the only patent on Mizoroki-Heck reactions in fluorous media by simple filtration (Table 15.1, entries 1, 2). The first two runs with iodobenzene and methyl acrylate at 100 °C in DMF were almost quantitative after 2 h reaction time (TON 5251), but after the third run at 100 °C the activity decreased (TON 2500-2900) and the authors changed the reaction time in the fourth run to 10 h to receive again quantitative conversion and yield (TON 5251). 

Another fluorous palladium complex that was applied in a Mizoroki-Heck reaction is the SCS pincer palladium complex 24 (Table 15.1, entry 3) [67]. It was applied under thermal and microwave heating. No fluorous solvent was used and the insoluble catalyst dissolved at the reaction temperature of 140 °C. The catalyst was recovered after 30 to 45 min by solid-phase extraction with a fluorous silica gel. Depending on whether activated or nonactivated substrates were coupled, the yields ranged between 76 and 94%. 

Curran, D.P., Fischer, K. and Moura-Letts, G. (2004) A soluble fluorous palladium complex that promotes Heck reactions and can be recovered and reused. Synlett, 1379-82. 

Fluorous ligands introduce an ease of purification in that the tagged phosphine ligand, the palladium catalyst complexed ligand, and the oxidized ligand can be completely removed by direct fluorous solid-phase separation (F-SPE) prior to product isolation. Similarly, an example of a fluorous palladium-catalyzed microwave-induced synthesis of aryl sulfides has been reported, whereby the product purification was aided by fluorous solid-phase extraction [91]. 

Figure 6.16. Aerobic oxidation of 1-phenylethanol catalysed by palladium complexes of a fluorous pyridine...

Fig. 6 Structure of the fluorous palladium PCP pincer complex lO-Rfs top, ORTEP representation middle, view with atoms at van der Waals radii bottom, packing diagram...

A fluorous palladium pincer complex for use in Heck reactions was reported by Curran (Reaction Scheme 11). The tridentate ligand ensnred stability under the high temperatures (140 °C) needed for the reaction to go to completion. The complex was recovered and rensed three times without any sign of lowered catalytic activity. 

Similar, fluorous palladium /i-dikctonatc complexes (27) have been employed for Wacker oxidation of olefins to the corresponding ketones in a biphasic system [27] (Scheme 3.10). 

Recently, the present authors have achieved a facile recycling method for both catalyst and reachon medium using F-626 in a Mizoroki-Heck arylation reaction of acrylic acids [11]. The procedure employed a fluorous carbene complex, prepared in situ from a fluorous imidazolium salt, palladium acetate as the catalyst and F-626 as a single reaction medium. When acrylic acid was used as a substrate, separation of the product from the reaction mixture was performed simply by filtration with a small amount of FC-72. The FC-72 solution containing the fluorous Pd-catalyst and F-626 was evaporated and the residue containing the catalyst and F-626 (96% recovery) can be recycled for the next run (Scheme 3.5-6). They tried to reuse the catalyst, and observed no loss of catalytic activity in five re-use cycles. 

Gladysz showed that a thermomorphic fluorous paUadacyde acts as a PdNP catalyst precursor for the Heck reaction at 80-140 C in DMF with very high turnover numbers [24a]. Molecular palladium complexes such as palladacycles and other palladium salts have also been used as PdNP precursors upon treatment with CO in DMF or toluene at room temperature, and these PdNPs catalyzed nudeophiUc substitution/carbonylation/amination affording iso-indolinones at room temperature [24bj. PdNPs capped with spedal ligands such as polyoxometal-... 

Schneider and Bannwarthhave developed fluorous triphenylphosphine-modified palladium complexes (11a—11c) for Stflle couplings in DMF/perfluoromefliylcyclo-hexane (1 1) using 1 equiv of LiCl as additive at 80 C for 3-24 h [Eq. (2)] [20]. 

Pozzi, Sinou, and co-workers prepared a fluorous chiral phosphine, (R)-2- bis[4-(1 H,1 H-perfluorooctyloxy)phenyl]phosphino -2 -(l H,1 H-perfluorooctyloxy)-l, 1 -binaphthyl (F content = 52%, partition coefficient n-perfluorooctane/toluene = 0.23, n-perfluorooctane/CHjOH = 7.42) and used for a chiral ligand of palladium complex in an asymmetric aUyHc alkylation of 1,3-diphenylprop-2-enyl acetate [8]. The reaction was carried out at room temperature in BTF or toluene and gave the corresponding product in 99% and 88% chemical yields and 81% ee and 87% ee, respectively after the nonfluorous MOP complex gave the product in 95% yield and 99% ee in toluene at 0 °C [9]) [Eq. (1)]. When toluene was used as a solvent, the simple extraction of the reaction mixture with n-perfluorooctane (twice) allowed the complete removal of the ligand and of the palladium complex. However, the recovered palladium complex did not have catalytic activity for the reachon. 

An easy recycling method involving both catalyst and reaction medium was achieved in a Mizoroki-Heck arylation reaction of acrylic acid, using a fluorous carbene complex (prepared in situ fl om a fluorous ionic liquid and palladium acetate) as the catalyst and a fluorous ether solvent (F-626) as the reaction medium. Because of the very low solubility of arylated carboxylic acids in F-626, the products precipitated during the course of the reaction. After separation of the products and amine salts by filtration, the filtrate, which contained the fluorous Pd catalyst, could be recycled for several runs (Scheme 13). The Mizoroki-Heck reaction was effectively promoted by a fluorous SCS pincer palladium, which is discussed in Section 3.4.5. 

Preparation of 4-methylacetophenone in the presence of a fluorous acetylacetonate palladium complex... 

Schneider and Bannwarth [25] have prepared three new perfluoro-tagged catalysts, which can be used in fluorous biphasic systems these can be recycled up to six times without significant reduction in yield. Several years ago, Mathey, Regitz, and coworkers [26] reported on the use of palladium complexes of a 10-membered tetraphosphane, which they suggested to be more cost effective than the... 

Pd(II), and Pt(II) (Scheme 7.9) [18]. The pincer palladium complex 21 was air-stable and able to efficiently catalyze the Heck reaction of methyl acrylate with aryl haHdes. The catalyst could be recovered by fluorous soHd-phase extraction and reused for four times without significant loss of catalytic activity. 

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