Fluorinated alcohol catalysts

Carboxylic acids do not react with phosgene easily, and the reactions require promotion with catalysts in order to avoid the need to use excessively high temperatures. The situation may be compared to the reactions of the highly acidic (for example fluorinated) alcohols. 

A recent improvement to this type of reaction often selects for the formation of tetroxanes over the trimeric hexaoxonane analogs. The use of fluorinated alcohols such as trifluoroethanol (TEE) or, often better, HFIP, as solvent and methyltrioxorhenium (MTO) as catalyst, as well as a substrate concentration of 1 M, are considered important for success (Equation (26) Table 3) <2003TL6309, 2006T1479, 2006BMC7790>. 

A review has illustrated the importance of atomic-level DFT studies in elucidation of the function of hydrogen bonds in organocatalytic reactions through influence on the mechanism of substrate activation and orientation, and the stabilization of transition states and intermediates. Examples discussed include stereoselective catalysis by bifunctional thioureas, solvent catalysis by fluorinated alcohols in epoxidation by hydrogen peroxide, and intra-molecular cooperative hydrogen bonding in trans-a,a -(dimethyl-l,3-dioxolane-4,5-diyl)bis(diphenyl methanol) (TADDOL) (7)-type catalysts. ... 

Since most common rhodium catalysts are poorly soluble in SCCO2, adaptation of either ligand or catalyst or the reaction medium has to be taken into account [71]. For example, the use of co-solvents (aliphatic alcohols, fluorinated alcohols) was recommended [72]. 

The high solubility of the MTO catalyst in almost any solvent opens up a broad spectrum of reaction media from vhich to choose when performing epoxidations. The most commonly used solvent, however, is still dichloromethane. From an environmental point of view this is certainly not the most appropriate solvent in large scale epoxidations. Interesting solvent effects for the MTO-catalyzed epoxida-tion were reported by Sheldon and coworkers, who performed the reaction in trifluoroethanol [86]. The change from dichoromethane to the fluorinated alcohol allowed for a further reduction of the catalyst loading down to 0.1 mol%, even for terminal alkene substrates. It should be pointed out that this protocol does require 60% aqueous hydrogen peroxide for efficient epoxidations. 

The first reports on the use of fluorinated alcohols, and in particular of HFIP in oxidations with hydrogen peroxide, can be found in the patent hterature of the late 1970s and early 1980s [19,20]. Typically, 60% aqueous hydrogen peroxide was used in the presence of metal catalysts. A number of reports on alkene epoxidations in fluorinated alcohols, both in the absence and in the presence of additional catalysts, have followed. 

In 2000, Neimann and Neumann reported on alkene epoxidation by H2O2 in fluorinated alcohol solvents without the addition of further catalysts [21]. Shortly thereafter, in 2001, Sheldon et al. reported about their results, also on alkene epoxidation in fluorinated alcohol solvents [22]. In the latter study, it became clear that buffering the reaction mixtures, preferably by addition of Na2H PO4 improves the overall efficiency of the process, presumably by suppressing acidotalyzed degradation of the product epoxides. Scheme 4.3 summarizes the results obtained using TFE as solvent, whereas the results for HFIP are summarized in Scheme 4.4. 

The catalysts applied to alkene epoxidation in fluorinated alcohol solvents can be subdivided into those which are metal/chalconide-based and those which are purely organic in nature (Scheme 4.5). The former comprise arsanes/arsane oxides [27,28], arsonic acids [29, 30], seleninic acids/diselenides ]31-35], and rhenium compounds such as Re207 and MTO (methylrhenium trioxide) ]36,37]. As shown in Scheme 4.5, their catalytic activity is ascribed to the intermediate formation of, for example, perseleninic/perarsonic adds or bisperoxorhenium complexes. In other words, their catalytic effect is due to the equilibrium transformation of hydrogen peroxide to kmetically more active peroxidic spedes. 

With regard to the mechanism, Jacobson et td. proposed that the arsonic acid catalyst is transformed to the perarsonic add by hydrogen peroxide, the perarsonic add being the active oxidant (Scheme 4.5) [29]. This may well be the case for arsonic add-catalyzed epoxidations performed in 1,4-dioxane as solvent When using fluorinated alcohols as solvent, we believe that reversible ester formation is involved in the mechanism (Scheme 4.7). This assumption is based on ESI-MS studies of the reaction mixtures [23]. 

Fluorinated alcohols, and in particular HFIP, have also proven beneficial for epoxidations of alkenes using persulfate (Oxone) as the terminal oxidant and fluoroketones as catalysts [9, 10]. Under these conditions, the fluorinated ketones are converted to dioxiranes, which are the active epoxidizing spedes. Typical catalysts... 

It was noted in Sections 4.3.2.2 and 4.3.2.3 that arsonic acids and seleninic adds are efficient catalysts for the epoxidation of alkenes. For both types of catalyst, significant enhancement of catalyst activity and selectivity was observed in fluorinated alcohol solvents compared to, for example, 1,4-dioxane. 

Otsuka, T. Ishii, A. Dub, P. A. Ikariya, T. Practical selective hydrogenation of a-fluorinated esters with bifunctional pincer-type mthenium(II) catalysts leading to fluorinated alcohols or fluoral hemiacetals. J. Am. Chem. Soc. 2013,... 

A. Saito, T. Ono, Y. Hanzawa, Cationic Rh(l) catalyst in fluorinated alcohol mild intramolecular cycloaddition reactions of ester-tethered unsaturated compounds, J. Org. Chem. 71 (2006) 6437-6443. 

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