Oxidation fluorous

Compounds lb and 2b were the Urst fluorinated ligands tested in Mn-catalyzed alkene epoxidation [5,6]. The biphasic Uquid system perfluorooc-tane/dichloromethane led to excellent activity and enantioselectivity (90% ee) in the epoxidation of indene with oxygen and pivalaldehyde (Scheme 1, Table 1). In addition, the fluorous solution of the catalyst was reused once and showed the same activity and selectivity. This represents a considerable improvement over the behavior in the homogeneous phase, where the used catalyst was bleached and reuse was impossible. Unfortunately, indene was the only suitable substrate for this system, which failed to epoxidize other alkenes (such as styrene or 1,2-dihydronaphthalene) with high enantioselectivity. The system was also strongly dependent on the oxidant and only 71% ee was obtained in the epoxidation of indene with mCPBA at - 50 °C. 

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]. 

Further efficient ligands for the epoxidation of alkenes have been reported by Pozzi, but using PhIO as the oxidant and pyridine V-oxide as an additive in FBS.[7, 51-53] Chiral (salen)Mn complexes have been synthesised, which are soluble in fluorous solvents and active in the epoxidation of a variety of alkenes. The catalysts were of the form shown in Figure 6.14. 

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

Pozzi has also reported a fluoro-functionalised tetraazacyclotetradecane macrocycle, which is selectively soluble in fluorocarbons and active in the fluorous biphasic oxidation of hydrocarbons. [59] This ligand (Figure 6.17) was produced whilst... 

Bayardon and Sinou have reported the synthesis of chiral bisoxazolines, which also proved to be active ligands in the asymmetric allylic alkylation of l,3-diphenylprop-2-enyl acetate, as well as cyclopropanation, allylic oxidations and Diels-Alder reactions. [62] The ligands do not have a fluorine content greater than 60 wt% and so are not entirely preferentially soluble in fluorous solvents, which may lead to a significant ligand loss in the reaction system and in fact, all recycling attempts were unsuccessful. However, the catalytic results achieved were comparable with those obtained with their non-fluorous analogues. 

A number of modifications of the structure of the allylstannane have been prepared with the aim of facilitating the removal of tin from the product. These include Curran s fluorous allylstannane (see Section 3.14.04.1), Pereyre s monoallylstannane AllylXSn[N(TMS)2]2 (Equation (92) above),258 allylstannanes with a polar (oligoethylene oxide) tail (e.g., 23 and 24), and the allylstannyl group bonded to a soluble or insoluble (cross-linked) polystyrene. The reaction using the allylstannane bonded to a soluble, uncross-linked, polystyrene resin occurs about 100 times faster than that on the cross-linked, insoluble resin, and the polymer can be recovered by recrystallization from methanol. 

A similar reaction has been conducted under fluorous biphasic conditions, using a perfluoroalkylated bipyridine as ligand to ensure that the copper species resides in the fluorous phase [22], The oxidation of a range of primary alcohols to the corresponding aldehydes was found to be possible, an example of which is shown in Scheme 9.11. The catalyst could be successfully recycled by phase separation, with analytically pure products being isolated even after... 

A fluorous analogue of DMSO has been used to perform Swern reactions [24], This widely used method of oxidizing an alcohol to an aldehyde falls down seriously from the environmental point of view due to its production of a stoichiometric amount of dimethyl sulfide. Here, a fluorous sulfoxide is prepared and used in the oxidation of several alcohols in dichloromethane, as shown in Scheme 9.12. After reaction, the sulfide is extracted into perfluorohexane and the system recycled. Unfortunately, extraction from dichloromethane was found to be difficult, but replacing the dichloromethane with toluene leads to a more efficient recovery. 

Aldehydes may be converted to carboxylic acids using Ni(acac)2 immobilized in [bmim][PF,5], with oxygen as the oxidant, as shown in Scheme 9.14 [27], A similar reaction has also been performed using perfluorinated solvents, and it was found that there was little difference between the two systems [28], However, the Ni(acac)2 catalyst could not be used directly in the fluorous solvent and therefore the 1,3-diketonate was modified with long perfluorinated chains prior to use to ensure solubility. 

In both the Ni(acac)2-[bmim][PF6] and fhtorous biphasic systems, catalyst leaching is very low and several further batch oxidation reactions may be carried out with similar results to those obtained in the first run. In the fluorous biphasic system, the yield of 4-chlorobenzoic acid dropped from 87 % to 70 % by the sixth reaction cycle using [bmim][PF6] as a solvent, the yield was essentially the same after four uses, and no catalyst was found to leach into the organic phase. 

Oxidation reactions are not limited to those that occur at a carbon centre. The perfluorinated Ni(F-acac)2-benzene-CgFi7Br system described above was also active for the oxidation of sulfides to sulfoxides and sulfones [28], A sacrificial aldehyde is required as co-reductant, but the reaction may be tuned by changing the quantity of this aldehyde. If 1.6 equivalents of aldehyde are used, the sulfoxide is obtained, whereas higher quantities (5 equivalents) lead to sulfones. Fluorous-soluble transition metal porphyrin complexes also catalyse the oxidation of sulfides in the presence of oxygen and 2,2-dimethylpropanal [29],... 

The ideal systems for these media are those which do not require any additional solvent, and in which the substrate is more soluble than the product, leading to preferential rejection of the product from the catalyst phase. For fluorous reactions, this would include oxidation reactions where oxygenated products are typically more polar than the substrates. In ionic liquids it is products less polar than the substrates that will normally be less soluble, although the ability to tune the structure of ionic liquids to match a particular application must... 

Neumann and Fish have studied the novel polyoxometalate salt 25, which features 12 fluorous ammonium cations [12]. This material was insoluble in EtOAc (and toluene) at room temperature, but dissolved at 80 °C to give an effective catalyst system for the oxidation of alkenes and alcohols by 30% aqueous H2O2. CooHng precipitated the catalyst, which was reused. Additional examples of thermomorphic fluorous catalysts have been briefly described in meeting abstracts [60,61] and will Hkely soon appear in the peer-reviewed literature. 

Fig. 23. This photograph shows a two-phase system consisting of (top phase) toluene and (bottom phase) perfluoro-2-butyltetrahydrofuran (Fluoroinert FC-75).The dark color (brown) in the bottom phase indicates that the dendrimer-encapsulated Pd nanoparticles, complexed with poly (hexafluoropropylene oxide-co-difluoromethylene oxide) monocarboxylic acid, are selectively extracted into the fluorous phase. No detectable color was observed in the organic phase. Reprinted with permission from Ref. 103 Copyright 2000 American Chemical Society...

The catalyst remains in the fluorous phase, whilst the product is completely extracted, and secondary alcohol can be prepared by H2O2 oxidation. The catalyst solution can be recycled several time without loss of activity. 

FIGURE 14. Phase behavior in the oxidation reaction with aqueous H2O2 catalyzed by (RFN+)i2[WZnM2(H20)2(ZnW9034)2] [M = Mn(II), Zn(II)] with and without fluorous solvents... 

Owing to its chemically highly aggressive nature, fluorine is difficult and hazardous to handle and it can be manufactured only via the electrolytic oxidation of fluoride. Fluorine gas has been produced commercially since 1946 and has found applications in many areas of fluorine chemistry (polymers, surfactants, lubricants, thermally stable liquids, blood replacement and pharmaceuticals, propellants, etc.). Inorganic fluorides such as Sp6 and UFe [21] have technical applications. Fluorous solvent systems [22] provide novel reaction environments fundamentally different from both aqueous and hydrocarbon media [23] and fluorine has been employed as a marker or spin label [24]. 

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