Isomerization of Epoxides to Ketones

Interestingly, the use of (S,S)-bis(l-phenyl)ethylamide as base with epoxide 70 predominantly yields ketone 71. Where the possibility for competing C-H insertion is removed (e. g., with epoxide 73), isomerization to ketone 74 occurs in excellent yield. 

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Isomerization has been observed with many a,j3-unsaturated carboxylic acids such as w-cinnamic 10), angelic, maleic, and itaconic acids (94). The possibility of catalyzing the interconversion of, for example, 2-ethyl-butadiene and 3-methylpenta-l,3-diene has not apparently been explored. The cobalt cyanide hydride will also catalyze the isomerization of epoxides to ketones (even terminal epoxides give ketones, not aldehydes) as well as their reduction to alcohols. Since the yield of ketone increases with pH, it was suggested that reduction involved reaction with the hydride [Co" (CN)jH] and isomerization reaction with [Co (CN)j] 103). A related reaction is the decomposition of 2-bromoethanol to acetaldehyde... 

Isomerization of epoxides to ketones.3 This radical cation [as well as trityl hexachlorostibnate, (C6H5)3C+SbCl6 ] effects this reaction. 

Recent results on the isomerization of epoxides to ketones accomplished via electrode-catalyzed, one electron-oxidizing reagents, and DCA-sensitized photoreaction under nitrogen atmosphere, seem to confirm this mechanistic pathway [142, 143]. On the other hand, the MCPBA oxidation of 42 affords the same reaction products 43, 44, through a plausible acid-catalyzed isomerization of the same intermediate 45 [144]. 

The proposed mechanism of the isomerization of polyfluorooxiranes to ketones does not involve a 1,2-fluorine shift, but rather coordination of the Lewis acid with the epoxide oxygen, ring opening to the carbocation, and intermolecular addition and elimination of fluoride.29 45... 

The most widely studied aspect of arene-oxide chemistry is the aromatization reaction to yield phenols. The acid-catalyzed, spontaneous, and thermal rearrangements of epoxides to ketones have a parallel in the isomerization of arene oxides to dienone intermediates with subsequent aromatization to phenols. Prior to their availability by chemical synthesis, arene oxides were postulated as initial inter-... 

The Beckmann rearrangement of ketoximes to the corresponding amides (31), the Fischer indole cyclization, isomerization of epoxides to the corresponding aldehydes, ketones, or alcohols, hydration and ammo-nolysis of epoxides, oxygen-sulfur interchange, formation of diaryl-ureas and -thioureas from condensation of aniline and carbonyl sulfide, and olefin carbonylation occur over zeolite catalysts (62). The oxo reaction over rhodium and cobalt containing zeolites recently has been claimed (22). 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

Catalysts based on palladium, such as 10% palladium on charcoal, have also been used frequently. In these cases ketones derived from isomerization of the epoxides are often obtained as by-products. As shown in Table 11, both product- and regio-selectivities are highly dependent on the configuration of the starting epoxides. Geneste et suggested that the selectivity may be controlled at the stage of the approach of epoxides to catalyst. 

The stereoselectivity of the aldol reaction was initially investigated using bromoacetone and benzalde-hyde, and it was found that THF is the best solvent for obtaining an optimum synianti ratio the syn-hro-mohydrin (65 precursor to cis-epoxide) predominates in a ratio of 81 19. When the 81 19 mixture of (65) and (66) was treated with triethylamine, the rmns-epoxide (68) was obtained exclusively in nearly quantitative yield (equation 21). After exploring several sets of reaction conditions aimed at avoiding the facile isomerization of (65) to the thermodynamically favored anti isomer (66), it was found that KF/di-cyclohexyl-18-crown-6 induces cyclization with a minimum amount of isomerization. The overall results for the process of Scheme 16 for several reactants are shown in Table 7. It was found that, in each case, cis-epoxy ketones are obtained with moderate to high stereoselectivity. 

Isomerization of epoxides. a, -Epoxy ketones and /S.y-epoxy nitroalkanes" undergo ring opening to give a-diketones and y-hydroxy nitroalkenes, respectively. 

Hydrogenation of epoxides lends itself well to both synthetic applications and mechanistic studies. The reaction is complex, for either carbon-oxygen bond may break with or without inversion of configuration, and the product may contain deoxygenated products (92,93) as well as ketones derived by isomerization (26). The reaction is especially sensitive to both catalyst and environment (74). 

Asymmetric hydrogenolysis of epoxides has received relatively little attention despite the utility such processes might hold for the preparation of chiral secondary alcohol products. Chan et al. showed that epoxysuccinate disodium salt was reduced by use of a rhodium norbornadiene catalyst in methanol/water at room temperature to give the corresponding secondary alcohol in 62% ee (Scheme 7.31) [58]. Reduction with D2 afforded a labeled product consistent with direct epoxide C-O bond cleavage and no isomerization to the ketone or enol before reduction. 

Downing et al. (1997) have reported a number of examples, including isomerization of 2,3-dimethyl-2,3-epoxide to methyl-rer/-butyl ketone, which is required for the production of photographic and crop-protection chemicals. 

Epoxides are reactive substrates, which can easily be isomerized to give aldehydes or ketones. Kulawiec and coworkers have combined a Pd-catalyzed isomerization of mono and diepoxide 6/1-348 or 6/1-349 and 6/1-352 or 6/1-353, followed by an aldol condensation to give either cyclopentenones or cyclohexenones 6/1-350, 6/1-351, 6/1-354 and 6/1-355, respectively (Scheme 6/1.89) [165]. 

A closer examination by ex situ analysis using NMR or gas chromatography illustrates that intrazeolite reaction mixtures can get complex. For example photooxygenation of 1-pentene leads to three major carbonyl products plus a mixture of saturated aldehydes (valeraldehyde, propionaldehyde, butyraldehyde, acetaldehyde)38 (Fig. 33). Ethyl vinyl ketone and 2-pentenal arise from addition of the hydroperoxy radical to the two different ends of the allylic radical (Fig. 33). The ketone, /i-3-penten-2-one, is formed by intrazeolite isomerization of 1-pentene followed by CT mediated photooxygenation of the 2-pentene isomer. Dioxetane cleavage, epoxide rearrangement, or presumably even Floch cleavage130,131 of the allylic hydroperoxides can lead to the mixture of saturated aldehydes. 

Styrenes [103], conjugated aT-dienes [107], and aT-enynes [108] are also epoxidized with ketones 57 in high ees (Table 5, entries 9-14). No isomerization of the epoxides was observed therefore only c/x-epoxides were obtained from cis-olefins. Alkenes and alkynes appear to be effective directing groups to favor the desired transition states T and V (Fig. 19). 

Epoxides derived from indene,21 1,2- and 1,4-dihydronaphtha lenc 1702 a,4-benzo-1,S cycloheptadicne, 68 and 3,4-benzo-l,3-cycIo-octodlene841 are a)) reported to undergo isomerization to ketones in the presence of magnesium bromide (Eq. 450). That the carbonyl function is separated in every instance from the benzene ring by a methylene group may be taken to indicate probable existence of an open car-bonium ion in these processes. Bing contraction has been noted in one... 

The epoxide-ketone rearrangement is not limited to polyfluorooxiranes. Michel and Schlosser have studied the isomerization of 2-fluorooxiranes to oc-fluoro ketones by the action of triethylamine trishydrofluoride.47 Thus, 2-substituted 2-fluorooxiranes 10 isomerize re-giosclectively to fluoromethyl ketones 11 when heated at 125 C. 

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