Epoxidation fluorinated alcohol solvent

As a third example for an organocatalytic reaction, based on multiple hydrogen bonding and mechanistically investigated by DFT, we selected olefin epoxidation with hydrogen peroxide in fluorinated alcohol solvents, such as 1,1,1,3,3,3-hex-afluoro-2-propanol (HFIP) (Scheme 8). Here we encounter a new type of catalytic hydrogen bond the cooperative hydrogen bond. 

Berkessel A, Adrio JA (2004) Kinetic studies of olefin epoxidation with hydrogen peroxide in l,l,l,3,3,3-hexafluoro-2-propanol reveal a crucial catalytic role for solvent clusters. Adv Synth Catal 346 275-280 Berkessel A, Adrio JA (2006) Dramatic acceleration of olefin epoxidation in fluorinated alcohols activation of hydrogen peroxide by multiple H-bond networks. J Am Chem Soc 128 13412-13420 Berkessel A, Adrio JA, Huttenhain D, Neudorfl JM (2006a) Unveiling the booster effect of fluorinated alcohol solvents aggregation-induced conformational changes, and cooperatively enhanced H-bonding. J Am Chem Soc 128 8421-8426... 

The epoxidation of alkenes is accelerated in fluorinated alcohol solvents the factors responsible for this rate acceleration have been examined <2006JA8421, 2006JA13412>. Chiral dioxiranes can now be used in a catalytic sense for the synthesis of vinyl m-epoxides <2006AGE4475>. 

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. 

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. 

In this example the solvent - a fluorinated alcohol - forms higher order aggregates and activates for the epoxidation of electron rich olefins. HFIP accelerates this oxidation reaction up to 100,000-fold (relative to that in 1,4-dioxane as solvent). Which hydrogen bond network involving olefin, and fluorinated alcohol gives rise to such spectacular accelerations ... 

Fluorous solvents proved to be highly effective in epoxidation of alkenes. H202 can be used in combination with trifluoroacetone,27 perfluoroacetone,28 or a mixture of perfluoroacetone and hexafluoro-2-propanol.29 In fluorinated alcohols as solvents uncatalyzed epoxidations with aqueous H202 are performed.30,31... 

Sheldon RA, van Vliet MCA, Arends IWCE (2001) Fluorinated alcohols effective solvents for uncatalysed epoxidations with aqueous hydrogen peroxide. Synlett 2001 248-250... 

Fluorinated acetone [179,180] forms adducts with hydrogen peroxide that are active in epoxidation. The adducts function at relatively high temperatures and use halogenated solvents. The use of fluorinated alcohols such as trifluoroethanol improves the performance [181]. 

Fluorinated alcohols, TFE and HFIP, have often been used as catalytic solvents for epoxidation reactions under mild conditions [34]. The merit of these fluorinated alcohols is, surely, their resistant nature toward oxidation. Another merit of their use in oxidation reactions has often been said to be their catalytic activities via protonation of an active oxygen species, such as H2O2. Experimental and computational studies indicate that the protonated hydrogen peroxide, H3C>2+, which is generated by the action of H2O2 with a strong acid, is a very powerful oxidant. In contrast, weak acids such as TFE appear to... 

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. ... 

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. 

As a consequence of the above summarized properties of fluorinated alcohols, they are ideal solvents for the generation of cationic or radical-cationic species or reaction intermediates. This eflect has been exploited numerous times, for example, in the investigation of organic radical cations [11]. At the same time, it lies at the heart of the catalysis of alkene epoxidation with hydrogen peroxide and of Baeyer-Villiger-type oxidations of carbonyl compounds. The mechanisms of the latter two reaction types are discussed in more detail in Sections 4.3.1.1 (epoxidation) and Section 4.5.1 (Baeyer-VUliger). 

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]. 

A detailed kinetic study using UV-vis, FTIR (Fourier-transform infrared), and NMR spectroscopy a Hammett plot with /0 = -h1.98 using para-substituted styrene oxides an inverse solvent kinetic isotope effect (KIE) (fcnHp/ HHP-d2) = 0.86 and nonlinear effects studies" have all shown that the (salen)Co- (J) and amidine-co-catalysed enantioselective ring opening of terminal- and mew-epoxides by fluoride ion (forming trans- -ttuoTO alcohols in a 42-89% yield with 84-99% ee) occurs by the mechanism shown in Scheme 5. /-BuOOH oxidizes the Co(H) to Co(III) in the (salen)Co(III) catalyst. PhCOF provides the fluorine for the reaction. 

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