Epoxidation of electron-deficient alkenes

The epoxidation ofa, (3-unsaturated ketones catalysed by polyamino acids is known as the Julia-Colonna epoxidation.This three-phase procedure utilises aqueous hydrogen peroxide as oxidant along with a water immiscible solvent and solid poly-L-leucine as a catalyst and is mainly effective in the epoxidation of chalcone (4.79) and derivatives.  

There have been several modifications of the Julia-Colonna procedure, most particularly by Roberts and coworkers, who have developed a two-phase system by performing the reaction in the absence of water. Replacement of aqueous 

This epoxidation proceeds by conjugate addition of hydroperoxide anion followed by cyclisation of the resulting enolate in similar fashion to the Wietz-Scheffer process. It is proposed that the polyamino acid, present as an a—helix, forms a simple active site near the N-terminus within which the epoxidation occurs, and that catalysis arises from stabilisation of the intermediate enolate by interaction with an oxy-anion hole formed within this active site. 

Lattanzi and coworkers have discovered that commercially available a,a-diphenylprohnol (4.93) catalyses the epoxidation of chalcone and derivatives with 

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The epoxidation of electron-deficient alkenes, particularly a,P-unsaturated carbonyl compounds, continues to generate much activity in the literature, and this has been the subject of a recent concise review <00CC1215>. Additional current contributions in this area include a novel epoxidation of enones via direct oxygen atom transfer from hypervalent oxido-).3-iodanes (38), a process which proceeds in fair to good yields and with complete retention of... 

Direct phase-transfer catalysed epoxidation of electron-deficient alkenes, such as chalcones, cycloalk-2-enones and benzoquinones with hydrogen peroxide or r-butyl peroxide under basic conditions (Section 10.7) has been extended by the use of quininium and quinidinium catalysts to produce optically active oxiranes [1 — 16] the alkaloid bases are less efficient than their salts as catalysts [e.g. 8]. In addition to N-benzylquininium chloride, the binaphthyl ephedrinium salt (16 in Scheme 12.5) and the bis-cinchonidinium system (Scheme 12.12) have been used [12, 17]. Generally, the more rigid quininium systems are more effective than the ephedrinium salts. 

Metal alkyl peroxides can be used for the epoxidation of electron-deficient alkenes such as enones. The use of a combination of diethylzinc, oxygen, and A-methylephedrine gave epoxides in very high yield and generally high enantio-selectivity (Figure 11.8). " ... 

The epoxidation of electron-deficient alkenes with either vanadium or titanium catalysts give syw-epoxides347 a free hydroxy group and a ketone or ester function are necessary for the reaction to take place, and a modest level of asymmetric induction can be achieved with y-hydroxy enone substrates and chiral titanium catalysts348. 

The base-catalysed epoxidation of electron-deficient alkenes was also described1157,1741 and proceeded with excellent conversions and selectivities, when the surface was passivated by silylation. Their high efficiency in the epoxidation of alken-2-one results from their ability to deprotonate H202 leading to an ion pair (HOO-, MTS-TBDH+) and from their lipophilic character, which favours the adsorption of olefin which then reacts via 1 -4 addition (Scheme 9.9). 

The catalysts were evaluated in two reactions - the base catalysed epoxidation of electron deficient alkenes),[15] and in the Linstead variation of the Knoevenagel condensation to give 3-nonenoic acid. This reaction utilises malonic acid, and leads to an unusual dehydration, giving the P/y-unsaturated acid, rather than the more typical a,P-enoic acid.[21-24] The product can be used as a precursor to the lactone, which is a flavour component of coconut oil. 

A number of chiral phase-transfer salts capable of catalyzing the epoxidation of electron-deficient alkenes have been developed. The molecular framework provided by the Cinchona alkaloids have appeared to be a useful starting... 

Naruta et al. [225, 226] designed the twin-coronet porphyrin ligands (62) and (63) with binaphthyl derivatives as chiral substituents (Figure 13). Each face of the macrocycle is occupied by two binaphthyl units and the ligand has C2 symmetry. Iron complexes of these compounds can be very effective catalysts in the epoxidation of electron-deficient alkenes. Thus, nitro-substituted styrenes are readily epoxidized in 76-96% ee [226]. The degree of enantioselectivity can be explained on the basis of electronic interactions between the substrate aromatic ring and the chiral substituents rather than on the basis of steric interactions. 

The epoxidation of electron deficient alkenes such as methyl methacrylate has also been carried out using reaction conditions similar to those shown in Eq. (15), and with a,p-unsaturated ketones alkaline hydrogen peroxide has been generated from UHP and affords good yields of epoxides. Pulegone gave a 50% yield of the epoxide and the result obtained with isophorone is shown in Eq. (16). 

An obvious extension of the application of metal alkyl peroxides for epoxidation of electron-deficient alkenes is to use chiral ligands on the metal for asymmetric epoxidations. However, this extension has only very recently met with success. 

Shibasaki has recently described a process for epoxidation of electron-deficient alkenes catalyzed by chiral lanthanoid-BINOL complexes (5-8 mol %) using ferf-butyl hydrogen peroxide [or cumene hydroperoxide (CMHP)] [56]. Epoxides were obtained in excellent yields and enantioselectivities as shown in Scheme 21. 

Figure 7. Base-catalyzed epoxidation of electron-deficient alkenes.

Epoxidation. For epoxidation of electron-deficient alkenes KF supported on alumina is a useful base. Moderate ee values are observed when unfunctionalized alkenes are epoxidized in the presence of a chiral borate derived from dimethyl tartrate. 

Supported guanidines are prepared via different routes, and their activity compared in two reactions of interest. The base-catalysed epoxidation of electron-deficient alkenes is described, and proceeds with excellent conversions and selectivities, when the surface is passivated by silylation. The Linstead variation of the Knoevenagel condensation is also described, and gives excellent conversions to partially decarboxylated products. 

Genski, T., Macdonald, G., Wei, X. et al. (1999) Epoxidation of electron deficient alkenes using /ert-butyl hydroperoxide and l,5,7-triazabicyclo[4.4.0]dec-5-ene and its derivatives. Synlett, 795-797 Genski, T. and Taylor, R.J.K. (2002) The synthesis of epi-epoxydon utilising the Baylis-Hillman reaction. Tetrahedron Letters, 43, 3573-3576 Quesada, E., Stockley, M. and Taylor, R.J.K. (2004) The first total syntheses of ( )-preussomerins K and L using 2-arylacetal anion technology. Tetrahedron Letters, 45, 4877-4881. 

Besides of these main types of the chiral TAA salts, numerous other chiral TAA salts and crown ethers acting as moderately enantioselective PT catalysts were reported. Chiral PTC was mostly used for enantioselective formation of chiral carbon centers via alkylation of carbanions (enolates), Michael addition, the Darzens reaction and other reactions of carbanions. There are also numerous examples of enantioselective PTC epoxidation of electron deficient alkenes (for review, see Ref 105). 

Fraile, J. M. Garcia, J. I. Mayoral, J. A. Sebti, S. Tahir, R. Modified Natural Phosphates Easily Accessible Basic Gatalyst for the Epoxidation of Electron-Deficient Alkenes. Green Chem. 2001,3,271-274. 

Fraile et al. reported the epoxidation of electron-deficient alkenes by H2O2 with LDH as catalyst. The activity of the LDH depends on the basicity of the... 

The asymmetric epoxidation of alkenes constitutes a powerful approach to enantiomerically enriched epoxides, a class of highly versatile intermediates in organic synthesis [1]. Various effective epoxidation systems have been developed, including epoxidation of allylic [2, 3] and homoallylic [4] alcohols, metalunfunctionalized alkenes [5-7], and the nucleophilic epoxidation of electron-deficient alkenes [8]. During the past 10-15 years, much effort has been devoted to chiral ketone-catalyzed asymmetric epoxidation (Scheme 3.1). The subject has been described in great detail in the first edition [9] and other reviews [10]. This chapter provides an update on progress in this area since the first edition [9]. 

Alkaline hydrogen peroxide is used for epoxidation of electron-deficient alkenes such as acrylic acids, and also for oxidation of alkylboranes to alcohols, the second step of hydroboration-oxidation. 

The asymmetric epoxidation of electron deficient alkenes like a,p-unsaturated esters, ketones and nitriles often is not efficient with the reagents suitable for electron rich systems. Prominent examples for the successful epoxidation of a,P-enones are the well-known Weitz-Scheffer epoxidation using alkaUne hydrogen peroxide or... 

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