Fluorous layer

The yields for reactions of unsubstituted terminal alkenes were lower than for substituted alkenes but they were still reasonable and could be increased further by increasing the aldehyde alkene ratio. Total conversions of substrate were reported with epoxide selectivity as high as 95% in some cases. The FBC system allows for a much higher substratexatalyst ratio (1000 1) than the non-fluorous epoxidation reported (20 1) previously. Recycling the fluorous layer once showed no reduction in conversion or selectivity. 

If nonvolatile liquids are to be used to avoid the problems associated with volatile organic solvents, then it is very desirable that there is some convenient way of recovering the reaction products from the liquid. This approach is used in the biphasic systems described in Chapters 2-5. In the fluorous biphase (Chapter 3), reagents and catalysts are fine-tuned by adding perfluoroalkyl chains, known as ponytails , to ensure that only those chemicals will mix with the fluorous layer. Purification is simply a matter of separating the two phases. Transition metal catalysts with fluorous ligands will remain in the fluorous phase, and the whole catalyst-solvent mixture may be reused for another batch of reactions, as shown schematically in Figure 1.20b. 

C. Brornotris[2-(perfluorohexyl)ethyl]tin. The fluorous phenyltin product (17.2 g, 13.9 mmol) and dry ether (80 mL) are transferred to a 250-mL, three-necked flask that had been dried in an oven and cooled to 0°C under argon. Bromine (0.71 mL, 14 mmol) is added dropwise over 30 min to the mixture. The addition rate is adjusted to keep the temperature between 0° and 1°C. The mixture is warmed to 25°C and stirred for 7 hr. The reaction mixture is transferred to a 250-mL, round-bottomed flask. The ether and excess bromine are removed under reduced pressure to leave a yellow oil. The oil is dissolved in FC-72 (75 mL) and transferred to a 250-mL separatory funnel. The bromine and bromobenzene by-products are removed by washing three times with methylene chloride (3 x 75 mL) leaving the fluorous layer colorless. The FC-72 is removed under reduced pressure to provide 15.8 g (12.7 mmol, 92%) of a colorless oil (Note 6). 

The synthesis of array L7 is reported in Fig. 8.22. Compound 8.38 was reacted simultaneously with amines (Mi, two representatives), aldehydes (Mi, five representatives), and isonitriles (Ms, two representatives) to give 10 compounds (not all the combinations were reacted). The reaction was performed in trifluoroethanol (TFE), another hybrid fluorous-organic solvent (step a. Fig. 8.22), and after evaporation of the TFE, the crude product 8.39 was purified by two-phase extraction between fluorous solvents and benzene (step b). After evaporation of the solvent, the fluorous tag was cleaved with TBAF (step c) and a triphasic extraction (step d, Eig. 8.22) was performed to remove the fluorosilane tag and acid 8.38-related impurities extracted into the fluorous layer. Excess TBAE and TBAE-related impurities partitioned into the acidic aqueous layer. Yields and purities of the synthetic protocol are reported together with the structures of the library members L7a-j in Table 8.2. 

Both complexes were able to catalyze the oxidation of jt-substituted methyl phenyl sulfides at a substrate/catalyst molar ratio of 100, with good sulfoxide selectivities (> 90%). It should be noted that FB reactions catalyzed by Mn-14 consistently afforded higher sulfoxide yields than homogeneous reactions catalyzed by Mn-13 (Table 4). Moreover, three consecutive recyclings of the fluorous layer were performed with no appreciable loss of catalytic activity and selectivity. 

In a CCI4 solution, porphyrin 15 showed increased chemical stability toward O2 and hydroperoxides with respect to TPPo. However, physical segregation into the fluorous phase was found to be the most important factor in reducing the incidence of degradation processes. In addition, the FB approach ensured the easy separation of the hydroperoxides from 15 at the end of the reaction. The fluorous layer containing the sensitizer (57-94% of the starting material-depending on reaction conditions) could be re-used without further treatments. 

The Ru-catalyzed epoxidation of tran -stilbene in the presence of NaI04 was carried out using a bipyridyl ligand with a fluorous ponytail at the 4 and 4 positions. As illustrated by the first equation in Scheme 8, a triphasic system comprising water, dichloromethane and perfluorooctane was employed in the reaction. The reaction was complete in 15 min at 0°C and tran -stilbene oxide 5 was obtained from the dichloromethane layer in a 92% yield. The fluorous layer, containing the catalyst, could be recycled for four further runs without any addition of RuCls. The same perfluoroalkyl-substituted bipyridyl ligand was used successfully in the copper(i)-catalyzed TEMPO (2,2, 6,6 -tetramethylpiperidine (V-oxyl)-oxidation of primary and secondary alcohols under aerobic conditions (Scheme 8, second equation). ... 

Using a fluorous palladacycle catalyst 10 originating from the corresponding fluorous Schiff base and palladium acetate, a fluorous Mizoroki-Heck reaction was achieved with an excellent turnover number (Scheme 12). A homogeneous catalytic reaction system was obtained when DMF was used as the solvent. After the reaction, perfluorooctyl bromide was added to facilitate the separation of DMF (containing the products and amine salts) from the catalyst phase. The resulting lower fluorous layer was condensed under vacuum and the catalyst residue was used in a second run. In this reaction, the palladacycle catalyst appears to act as a source of palladium nanoparticles, which are thought to be the dominant active catalyst. 

An asymmetric hydrogen transfer of ketones was reported using chiral perfluorinated ligands in a 2-propanol/n-perfluooctane biphasic system. Several perfluorinated salen and diamine ligands were examined for the reaction catalyzed by the [Ir(COD)Cl]2 complex diamine 16 was found to be most effective (Scheme 20). The reaction was carried out at 70" C for 30 min and then the mixture was cooled to 0°C. The perfluorooctane solution was separated and used for the next reaction. The reactivity was almost the same as that of the first mn, and the enantioselectivity was higher (79% ee). Two further recyclings of the fluorous layer yielded the product with enantioselectivities up to 59% ee, but a decrease in activity was observed. 

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