Formation of epoxides

Results of stereochemical studies with various halohydrins confirm that the oxy-anion attacks the carbon from the opposite side, causing Walden inversion the erythro forms of 3-bromo-2-butanol, stilbene bromohydrin, and chloro malic acid give the trans oxide, and the corresponding threo forms lead to the cis oxides [146]. Furthermore, the frans-halohydrin of cyclohexene reacts 150 times as fast with OH- as the cis compound. Only the reaction of the trans compound yields an epoxide [147] in the reaction of the cis compound, an enol is formed first which then rearranges to the corresponding ketone [148, 149]. 

Consequently, the second step of the Winstein—Lucas mechanism must be a simple SN 2 substitution. On the other hand, a concerted (one-step) mechanism 

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Hydroxylation of terminal (syfluoroalkenes is accomplished by a mixture of hydrogen peroxide and formic add. The first step obviously is the formation of epoxide followed by nng opening [28] (equation 10)... 

The reactions of diazomethane with heterocycles containing a ketonic grouping in the ring do not differ, in principle, from those of alicyclic ketones (see footnotes 3 and 177) ring expansion and the formation of epoxides compete. In general, ring expansion is the more important reaction for example, tetrahydropyran-4-one (99) is converted to l-oxacycloheptan-4-one (100) (60%) and 4,4 -epoxy-4-methyltetrahydropyran (101) (23%). ... 

There are several available terminal oxidants for the transition metal-catalyzed epoxidation of olefins (Table 6.1). Typical oxidants compatible with most metal-based epoxidation systems are various alkyl hydroperoxides, hypochlorite, or iodo-sylbenzene. A problem associated with these oxidants is their low active oxygen content (Table 6.1), while there are further drawbacks with these oxidants from the point of view of the nature of the waste produced. Thus, from an environmental and economical perspective, molecular oxygen should be the preferred oxidant, because of its high active oxygen content and since no waste (or only water) is formed as a byproduct. One of the major limitations of the use of molecular oxygen as terminal oxidant for the formation of epoxides, however, is the poor product selectivity obtained in these processes [6]. Aerobic oxidations are often difficult to control and can sometimes result in combustion or in substrate overoxidation. In... 

The Sharpless-Katsuki asymmetric epoxidation (AE) procedure for the enantiose-lective formation of epoxides from allylic alcohols is a milestone in asymmetric catalysis [9]. This classical asymmetric transformation uses TBHP as the terminal oxidant, and the reaction has been widely used in various synthetic applications. There are several excellent reviews covering the scope and utility of the AE reaction... 

Epoxidation systems based on molybdenum and tungsten catalysts have been extensively studied for more than 40 years. The typical catalysts - MoVI-oxo or WVI-oxo species - do, however, behave rather differently, depending on whether anionic or neutral complexes are employed. Whereas the anionic catalysts, especially the use of tungstates under phase-transfer conditions, are able to activate aqueous hydrogen peroxide efficiently for the formation of epoxides, neutral molybdenum or tungsten complexes do react with hydrogen peroxide, but better selectivities are often achieved with organic hydroperoxides (e.g., TBHP) as terminal oxidants [44, 45],... 

The epoxidation method developed by Noyori was subsequently applied to the direct formation of dicarboxylic acids from olefins [55], Cyclohexene was oxidized to adipic acid in 93% yield with the tungstate/ammonium bisulfate system and 4 equivalents of hydrogen peroxide. The selectivity problem associated with the Noyori method was circumvented to a certain degree by the improvements introduced by Jacobs and coworkers [56]. Additional amounts of (aminomethyl)phos-phonic acid and Na2W04 were introduced into the standard catalytic mixture, and the pH of the reaction media was adjusted to 4.2-5 with aqueous NaOH. These changes allowed for the formation of epoxides from ot-pinene, 1 -phenyl- 1-cyclohex-ene, and indene, with high levels of conversion and good selectivity (Scheme 6.3). 

In a recent screening of different metal salts, Lane and Burgess found that simple manganese(n) and (in) salts catalyzed the formation of epoxides in DMF or t-BuOH in the presence of aqueous hydrogen peroxide (Scheme 6.7) [68]. It was further established that the addition of bicarbonate was of importance for the epoxidation reaction. 

A breakthrough in the area of asymmetric epoxidation came at the beginning of the 1990s, when the groups of Jacobsen and Katsuki more or less simultaneously discovered that chiral Mn-salen complexes (15) catalyzed the enantioselective formation of epoxides [71, 72, 73], The discovery that simple achiral Mn-salen complexes could be used as catalysts for olefin epoxidation had already been made... 

Another possibility is that the intermediate may be stable or may find some other way to stabilize itself. In such cases, Y never attacks at all and the product is cyclic. These are simple internal Sn2 reactions. Two examples are formation of epoxides and lactones ... 

Yn J, HE Jeffries (1997) Atmospheric photooxidation of alkylbenzenes. II. Evidence of formation of epoxide intermediates. Atmos Environ 31 2281-2287. 

The activities of both haloalkanol dehalogenase (halohydrin hydrogen lyase) that catalyzes the formation of epoxides from alkanes with vicinal hydroxyl and halogen groups, and epoxide hydrolase that brings about hydrolysis of epoxyalkanes to diols are involved in a number of degradations that involve their sequential operation. 

Cunninghamella elegans metabolized 1-fluoronaphthalene to a number of products whose synthesis was clearly initiated by the formation of epoxides and trani-dihydrodiols (Figure 9.28) (Cerniglia et al. 1984). This illustrates the apparent indifference of the monooxygenase to the presence of fluorine atoms. 

Another difference between dimethylsulfonium methylide and dimethylsulfoxonium methylide concerns the stereoselectivity in formation of epoxides from cyclohexanones. Dimethylsulfonium methylide usually adds from the axial direction whereas dimethylsulfoxonium methylide favors the equatorial direction. This result may also be due to reversibility of addition in the case of the sulfoxonium methylide.92 The product from the sulfonium ylide is the result the kinetic preference for axial addition by small nucleophiles (see Part A, Section 2.4.1.2). In the case of reversible addition of the sulfoxonium ylide, product structure is determined by the rate of displacement and this may be faster for the more stable epoxide. 

Alkylperoxyl radicals produced by addition reactions can be destructively isomerized with the formation of epoxides [13,139,154,155] ... 

Peracids react heterolytically with olefins with the formation of epoxides by the Prilezhaev reaction. So, the co-oxidation of aldehydes with olefins has technological importance. Peracids react with ketones with formation of lactones. These reactions will be discussed in Section 8.2. The oxidation of aldehydes are discussed in monographs [4-8]. 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

The formation of epoxides from oxygen appears to be a free radical process. 

The stepwise formation of epoxides through the reaction of alkenes with sodium hypochlorite with, or without, the isolation of the intermediate chlorohydrin has been subjected to catalysis with (V-benzylquininium chloride under liquiddiquid two-... 

Highly regioselective cyclizations of 3,4-, 4,5- and 5,6-unsaturated alcohols to yield tetrahydrofuranols and tetrahydropyranols have been carried out with the TS-I-H2O2 system (this is a titanium silicate molecular sieve-H202 complex.) The reactions involve the intermediate formation of epoxides and their Ni ring opening. 

Scheme 60 Catalytic asymmetric formation of epoxides from a,p-unsaturated ketones...

Laboratory scale bromination of alkenes in homogeneous solution using an undivided cell is adaptable to the formation of epoxides, bromohydrins or dibromides depending on the conditions [64]. Epoxides are generated using an initially neutral solution and a low concentration of bromide ions. The reaction sequence is similar to that of Scheme 2.3. Formation of bromohydrins requires dilute hydrobromic acid as the supporting electrolyte. Dibromides are obtained using a concentrated solution of sodium bromide as electrolyte. 

A conversion typical of a-halo-a-lithioaUcanes is the formation of epoxides that results from their reaction with aldehydes or ketones. As illustrated in equation 61, the bromo-lithium carbenoid is usually generated by halogen-lithium exchange. The intermediate lithium aUcoxide 113 undergoes an in situ ring closure to give the oxirane 114 . 

Numerous studies have been directed toward expanding the chemistry of the donor/ac-ceptor-substituted carbenoids to reactions that form new carbon-heteroatom bonds. It is well established that traditional carbenoids will react with heteroatoms to form ylide intermediates [5]. Similar reactions are possible in the rhodium-catalyzed reactions of methyl phenyldiazoacetate (Scheme 14.20). Several examples of O-H insertions to form ethers 158 [109, 110] and S-H insertions to form thioethers 159 [111] have been reported, while reactions with aldehydes and imines lead to the stereoselective formation of epoxides 160 [112, 113] and aziridines 161 [113]. The use of chiral catalysts and pantolactone as a chiral auxiliary has been explored in many of these reactions but overall the results have been rather moderate. Presumably after ylide formation, the rhodium complex disengages before product formation, causing degradation of any initial asymmetric induction. 

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