Epoxidation of simple alkenes

In aqueous medium the reaction occurs in heterogeneous phase, but this does not affect the reactivity, which, on the contrary, is sometimes higher than in homogeneous organic phase. For instance, the reactivity of cyclohexene with MCPBA in water is comparable to that in DCM and is 8 and 16 times higher than in biphasic medium and in homogeneous -hexane solution, respectively. 

Epoxidation in water allows the perhydroxylation of the carbon-carbon double bond to be achieved by a one-pot procedure [11]. The process is completely stereospecific and 1,2-diols are generally obtained in excellent yield  

The direct epoxidation of simple alkenes by H2O2 requires that the peroxide must be activated. In buffered aqueous tetrahydrofuran (THF), 50% H2O2 activated by stoichiometric amounts of organophosphorus anhy- 

Neumann and Miller [13] catalyzed the epoxidation of alkenes by 30% aqueous H2O2 with an insoluble catalytic assembly consisting of a silicate xerogel covalently modified with phenyl groups and quaternary ammonium polyoxometallate ion pairs as catalytically active species. The combined presence of phenyl units and the use of the octyldimethyl-substituted ammonium salt and [WZnMn2 (ZnW9034)2] as anionic polyoxometallate gives the best results. 

The water-soluble weso-tetrakis(4-JV-methylpyridyl)porphinatoman-ganese(lll) chloride efficiently catalyzes (2 m in at r.t., 99% conversion) the epoxidation of sodium 4-styrenesulfonate by oxone (a stable water-soluble oxidant with the approximate composition K2S04 2KHS05 KHS04) in water at neutral pH [15]. In the absence of catalyst, the reaction time is ca. 10 times longer. 

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Although the Sharpless catalyst was extremely useful and efficient for allylic alcohols, the results with ordinary alkenes were very poor. Therefore the search for catalysts that would be enantioselective for non-alcoholic substrates continued. In 1990, the groups of Jacobsen and Katsuki reported on the enantioselective epoxidation of simple alkenes both using catalysts based on chiral manganese salen complexes [8,9], Since then the use of chiral salen complexes has been explored in a large number of reactions, which all utilise the Lewis acid character or the capacity of oxene, nitrene, or carbene transfer of the salen complexes (for a review see [10]). 

TABLE 7. Summary of the reaction barriers (kcal mol for the epoxidation of simple alkenes with peroxyformic acid (PFA) and dimethyldioxirane (DMDO)... 

The most convincing evidence for an essentially synchronous peracid epoxidation of simple alkenes came from a combined experimental and theoretical study by Singleton, Honk and coworkers. Experimental KIEs for the reaction of m-CPBA with 1-pentene, determined by the clever methodology developed by Singleton and Thomas utilizing the combinatorial high-precision determination of C and H KIEs at natural abundance, confirmed the symmetrical or nearly symmetrical nature of this epoxidation TS. These data were corroborated by B3LYP/6-31G calculations on propylene that supported a synchronous transition state for peroxyformic acid epoxidation. 

In 1994, Mansuy and coworkers found that a simple ammonium salt, like ammonium acetate alone, is a very efficient cocatalyst for the metalloporphyrin-catalyzed epoxidation of simple alkenes by hydrogen peroxide ". Bases like sodium carbonate, sodium acetate or tetrabutylammonium hydroxide turned out to promote the porphyrin-catalyzed epoxidation without any other additive. Adducts of hydrogen peroxide (with Na2C03, urea, MesNO, PhsPO), which turned out to be particularly useful for reactions in which the concentration of H2O2 in solution needs to be controlled at a fixed level, have been employed by Johnstone and coworkers. 

Oxidations. The reagent 1 oxidizes primary and secondary alcohols to carbonyl compounds in fair to good yield. It is not useful for epoxidation of simple alkenes, but it epoxidizes allylic alcohols to form a,/ -epoxy alcohols in 60-70% yield, In general, this epoxidation is more stcreospccific than that observed with r-butyl hydroperoxide in combination with Mo(CO)6 (9, 81-82). 

Enantioselective epoxidation of simple alkenes is not easily achieved by reactions with alkylperoxy-Ti intermediates, however, cationic Pt(II)... 

If we consider the d0 metal-N,JV-dialkylhydroxylamino complexes (79), (80) and (81) as valid models for the reactive but unstable alkyl peroxide species Mo02(OOR)2, VO(OOR)3 or V203(00R)4, and Ti(OOR)4 presumably involved in catalytic oxidations, the low activity of vanadium and titanium for the epoxidation of simple alkenes could be interpreted by the fact that these alkenes cannot displace the O.O-bonded alkyl peroxide groups in the coordinatively saturated Vv- and Tiiv-alkyl peroxide species, whereas allylic alcohols can displace the alkyl peroxide groups by forming bidentate allylic alkoxides as in equation (75).162... 

Stabilizing the transition state when the epoxidation is occurring syn. This hydrogen bond means that peroxy-acid epoxidations of alkenes with adjacent hydroxyl groups are much faster than epoxidations of simple alkenes, even when no stereochemistry is involved. 

It is all true. Evidence that a silyl group stabilizes the S 2 transition state comes from the reactions of the epoxides of vinyl silanes. These compounds can be made stereospecifically with one equivalent of a buffered peroxy-acid such as m-CPBA. Epoxidation is as easy as the epoxidation of simple alkenes. You will see in a moment why acid must be avoided. 

Iron-mediated oxygen transfer is also at play in the chloroperoxidase (CPO) catalyzed epoxidation of simple alkenes, which has the added advantage of providing high enantiomeric excesses. For example, c/s-2-heptene 35 is converted to the chiral epoxide 36 in 78% yield. However, the protocol is generally limited to fairly accessible disubstituted alkenes the more imbedded olefin of cis-3-heptene only undergoes 12% conversion, while the epoxides derived from terminal olefins tend to alkylate the enzyme and serve as suicide inhibitors <0374701>. 

Enantioselective Epoxidations of Simple Alkenes with Metal-Containing Reagents... 

Further examples of molybdenum-catalyzed asymmetric epoxidations of simple alkenes have been reported by Otsuka and co-workers21 who described a reagent derived from tert-butyl hydroperoxide, chelated with molybdenum oxide and (-f)-diisopropyl tartrate. 

Other Applications. Other (/ ,/ )-stilbenediamine derivatives have been used to direct the stereochemical course of alkene dihydroxylation (with stoichiometric quantities of Osmium Tetroxide and epoxidation of simple alkenes with Sodium Hypochlorite and manganese(III) complexes. ... 

Due to the demand for inexpensive anti-HIV agents, several reactions for the synthesis of Indinavir (70, an HIV protease inhibitor of Merck Co.) have been reported. Enantioselective epoxidation of simple alkenes with bleach is achievable in the presence of the Mn " complex 69 possessing a well-designed chiral salen ancillary [69]. Scheme 20 exemplifies its application to the synthesis of Indinavir (70), by way of indene oxide (68) in 88 % ee [69]. This method is also useful for the asymmetric synthesis of a chromene epoxide in 97 % ee serving as an intermediate for Lemakalim, a K" -channel opening agent [70]. 

Perhaps the most common method for the epoxidation of simple alkenes is their reaction with peroxyacids, which has occasionally been referred to as the Prilezhaev (Prileschajew) reaction. O This reaction does not require transition metal catalysis and the yield of epoxide is often high. Peroxyacids such as 156 are prepared by reaction of carboxylic acids with hydrogen peroxide. An equilibrium is established during the reaction that favors the peroxyacid, although several alternative methods are available.279 in general, strong... 

Mn(III) sits neatly in a tetracoordinate pocket in the ligand, and catalyses the epoxidation of simple alkenes by sodium hypochlorite, NaOCl, ordinary domestic bleach. Best results are obtained when the alkenes are cis (although an alternative range of ligands, developed by Tsutomu Katsuki, work well with trans alkenes), and one of the most significant applications of the Jacobsen epoxidation is with indene, which gives an epoxide in 84% ee with <1% of the catalyst. The mechanism of the reaction is complex and not fully understood, although it probably involves a Mn(V) oxo species and may involve radical intermediates. 

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