Recycling fluorous catalysts

Aldol reaction. Triflyl and nonaflyl derivatives of (5)-(2-pyirolidinyl)methylamine mediate asymmetric aldol reactions in aqueous media/ The latter is a typically recyclable fluorous catalyst ... 

Besides rising to the challenge of developing new methods for recycling fluorous catalysts, there are also many reports... 

The most important biphasic liquid systems are probably those that combine a conventional organic phase with another type of solvent, such as water, a fluorous organic solvent, or an ionic liquid [3]. In those cases the solvent can be considered as the support for the catalyst phase and we have therefore limited the examples in this review to those where the recycled liquid catalyst phase is recovered as a whole. 

To be fair, it should be realized that if a catalyst must be recycled for economic reasons, the recycling efficiency compared to the nonfunctionalized catalyst must be higher in order to compensate for the increased price of the fluorous catalyst itself. However, every recycling technique has its own cost that must be evaluated for each specific case. 

Although the imidazolidinone catalysts used within these transformations are simple, cheap, readily accessible and in some cases recyclable using acid/base extraction, considerable efforts have been made to examine alternative methods to separate and recycle the catalyst with good success. Examination of the structure of imidazolidinone 22 shows two convenient points for the introduction of a polymer or fluorous support, R and R, both of which have been examined (Fig. 4). Curran has shown that identical reactivity, diastereoselectivity and enantioselectivity can be obtained using a fluorous tag (23) [53]. The catalyst can easily be recovered and recycled using F-SPE with excellent yield, purity and levels of activity. Polymer- (24) and silica-supported (25) imidazolidinones reported by Pihko [54] (R substitution)... 

The enantioselective synthesis of a-amino acids employing easily available and reusable chiral catalysts or reagents presents clear advantages for large-scale applications. Accordingly, recyclable fluorous chiral phase-transfer catalyst 31 has been developed by the authors group, and its high chiral efficiency and reusability demonstrated in the asymmetric alkylation of 2. After the reaction, 31 could be easily recovered by simple extraction with FC-72 (perfluorohexanes) as a fluorous solvent and used for the next run, without any loss of reactivity and selectivity (Scheme 5.17) [23]. 

Systems have been developed that allow the recycling of catalysts. The first case study involved simple adsorption of proline onto silica gel [6], but the system suffered from a loss in enantioselectivity. More recently, promising results have been obtained with fluorous proline derivatives [64] used for aldol reactions the recycling of fluorous catalysts has been demonstrated using fluorous solid-liquid extraction. Solid phase-supported catalysts through covalent bonds [65] and through noncovalent interactions [66] were also used for aldol reactions. Proline and other catalysts can be recycled when ionic liquids or polyethylene glycol (PEG) were used as reaction solvents [67]. 

Fig. 4. Schematic diagram of a fluorous biphase process in which a fluorous solvent and fluorous catalyst are recycled together.

Stoichiometric oxidation with Se02 became more attractive after Sharpless showed that the reaction could be carried out with catalytic amounts of Se02 and TBHP as the (re)oxidant [106]. The reaction involves an oxometal mechanism (see Fig. 4.39). The use of fluorous seleninic acids with iodoxybenzene as oxidant introduces the possibility of recycling the catalyst [107]. 

Fig. 9.27 Catalyst-on-Teflon-tape for recycling of fluorous catalysts.

Alternatively, an insoluble fluorous support, such as fluorous silica [43], can be used to adsorb the fluorous catalyst. Recently, an eminently simple and effective method has been reported in which common commercial Teflon tape is used for this purpose [44]. This procedure was demonstrated with a rhodium-catalyzed hydrosilylation of a ketone (Fig. 9.27). A strip of Teflon tape was introduced into the reaction vessel and when the temperature was raised the rhodium complex, containing fluorous ponytails, dissolved. When the reaction was complete the temperature was reduced and the catalyst precipitated onto the Teflon tape which could be removed and recycled to the next batch. 

An interesting effect is seen when FBSs are exposed to pressures of carbon dioxide. Pressures of between 16 and 50 bar can cause many such systems to become monophasic at room temperature and this may have applications in future separations. Related to this is the use of carbon dioxide pressure as a switch for recycling a fluorous catalyst on a fluorinated silica support. 

The first example of a fully recyclable fluorous chiral metal-free catalyst was reported by Maruoka and coworkers, who described the enantioselective alkylation of a protected glycine derivative (Scheme 5.17) with various benzyl- and alkyl bromides, in the presence of the quaternary ammonium bromide 62 as a phase-transfer catalyst [77]. Reactions were performed in a 50% aqueous KOH/toluene biphasic system in which 62 was poorly soluble. Nevertheless, the alkylated products were obtained in good yields (from 81 to 93%), with enantioselectivity ranging from 87 to 93% ee. Catalyst 62 was recovered by extraction with FC-72, followed by evaporation of the solvent, and could be used at least three times without any loss of activity and selectivity. 

The most appealing feature of fiuorous chiral catalysts is their easy separation from the reaction products, and possible recycling. To this end, emphasis was initially placed on the FBS approach, which is only effective for heavy fluorous catalysts with high or at least moderate partition coefficients in perfluorocarbons. Besides being synthetically demanding, heavy fiuorous chiral catalysts can exhibit unpre-dictably low activities and stereoselectivities, even after careful optimization of the FBS reaction conditions. These seem to be less-compelling issues for relatively simple hght fiuorous chiral catalysts that can be quickly evaluated under the... 

Scheme 11.7 Recyclable fluorous chiral phase-transfer catalyst.

For typical fluorous biphase catalysis the most important aspect is the simple recycling and re-use of the catalyst. Fluorous solvents have one special advantage over hydrocarbon solvents, however. Their very high oxygen dissolving capacity, combined with their extreme resistance to oxidative decomposition makes perfluorocarbons in combination with fluorous catalysts the optimum choice for oxidation reactions. Thus, the biomimetic oxidation of olefins with molecular oxygen and 2-methylpropanal as a co-reductand has been achieved with a fluorous cobalt porphyrin catalyst (22) [23], and also even without catalyst [24] (Scheme 3.7). 

Another industrially important oxidation reaction, the Baeyer-Villiger oxidation [28] of ketones to esters by 35% aqueous hydrogen peroxide as oxidant, can also be advantageously conducted in a fluorous biphasic medium [29]. When the recyclable fluorous Letvis acidic tin(IV) complex (28) is used as catalyst very high selectivity of conversion of ketones to the corresponding esters or lactones is achieved (Scheme 3.11). 

The Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides is a useful tool for carbon—carbon bond formation, and has found wide employment in areas such as natural product synthesis, the pharmaceutical industry, and material sciences. Novel recyclable Pd catalysts with fluorous ponytails in the ligand 2,2 -bipyridine were reported in a copper-free Pd-catalyzed Sonogashira reaction in a fluorous biphasic system (FBS) (Equation 4.19). The catalysts are only soluble in perfluorinated solvents at room temperature [41],... 

In an attempt to improve the ability to recycle the catalyst, fluorous versions of the oxazaborolidine have been constructed.12 Pre-catalyst 29 could be prepared in five steps. This species was able to form the requisite chiral catalyst 30 in situ. Ketones 31 could be reduced to alcohols 32 in good to excellent chemical and optical yields. It was noted that aryl... 

As expected, 1 is more active than 4, and is recovered in quantitative yield by extraction with perfluoromethylcyclohexane. Although 2 and 3 are more active than 4, they cannot be recovered by extraction with any fluorous solvents. The amide condensation proceeds cleanly in the presence of 5 mol% of 1 the desirable amide has been obtained in 95% yield by azeotropic reflux for 15 h. In addition, the corresponding N-benzylamide has been obtained in quantitative yield by heating 4-phenylbutyric acid with benzylamine in the presence of 2 mol% of 1 under azeotropic reflux conditions for 4 h. Based on these results, the re-use of 1 has been examined for the direct amide condensation reaction of cyclohexanecarboxylic add and benzylamine in a 1 1 1 mixture of o-xylene, toluene, and perfluorodecalin under azeotropic reflux conditions with removal of water for 12 h [ Eq. (2) and Table 2] [5]. After the reaction has been completed, the homogeneous solution is cooled to ambient temperature to be separated in the biphase mode of o-xylene-toluene/ perfluorodecalin. The corresponding amide is obtained in quantitative yield from the organic phase. Catalyst 1 can be completely recovered from the fluorous phase and re-used in the recyclable fluorous immobilized phase. 

---