Epoxidation of Simple Olefins

The asymmetric oxidation of indene to the corresponding epoxide (Equation 24) is carried out commercially by Sepracor on a small scale. Chiral indene oxide is an intermediate in the synthesis of crixivan (an HIV protease inhibitor). Reaction is carried out at 5°C with moderately high turnover numbers in the presence of an exotic donor ligand ( P3NO , 3-phenylpropylpyridine N oxide) and sodium hypochlorite as the terminal oxidant. A similar epoxidation of a simple cis olefin (Equation 25) leads to an enantiomerically pure amino-alcohol used in the synthesis of taxol, a potent anticancer drug. 

A so far still unsolved problem is the direct enantioselective epoxidation of simple terminal olefins. For example the epoxidation of propylene that was achieved with a 41% ee almost twenty years ago by Strukul and his coworkers using Pt/diphosphine complexes is still unsurpassed. Unfortunately such low ee s are of no practical interest. The problem was circumvented by Jacobsen using hydrolytic kinetic resolution of racemic epoxides (Equation 26) and is practised on a multi 100 kg scale at Chirex. The strategy used is to stereose-lectively open the oxirane ring of a racemic chiral epoxide leaving the other enantiomer intact. Reactions are carried out to a 50% maximum conversion. The catalyst belongs to the metal-salen class described above and can be recycled. The products are separated by fractional distillation. 

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One problem associated with the peroxotungstate-catalyzed epoxidation system described above is the separation of the catalyst after the completed reaction. To overcome this obstacle, efforts to prepare heterogeneous tungstate catalysts have been conducted. De Vos and coworkers employed W catalysts derived from sodium tungstate and layered double hydroxides (LDH - coprecipitated MgCU, AICI3, and NaOH) for the epoxidation of simple olefins and allyl alcohols with... 

The observation that addition of imidazoles and carboxylic acids significantly improved the epoxidation reaction resulted in the development of Mn-porphyrin complexes containing these groups covalently linked to the porphyrin platform as attached pendant arms (11) [63]. When these catalysts were employed in the epoxidation of simple olefins with hydrogen peroxide, enhanced oxidation rates were obtained in combination with perfect product selectivity (Table 6.6, Entry 3). In contrast with epoxidations catalyzed by other metals, the Mn-porphyrin system yields products with scrambled stereochemistry the epoxidation of cis-stilbene with Mn(TPP)Cl (TPP = tetraphenylporphyrin) and iodosylbenzene, for example, generated cis- and trans-stilbene oxide in a ratio of 35 65. The low stereospecificity was improved by use of heterocyclic additives such as pyridines or imidazoles. The epoxidation system, with hydrogen peroxide as terminal oxidant, was reported to be stereospecific for ris-olefins, whereas trans-olefins are poor substrates with these catalysts. 

The resulting material is active for the gas phase epoxidation of simple olefins. Addition of cyclohexene resulted in the formation of cyclohexene oxide as the sole volatile product, detected by GC/MS. 

Catalytic Enantioselective Epoxidation of Simple Olefins by Salen Complexes... 

Although salen complexes of chromium, nickel, iron, ruthenium, cobalt, and manganese ions are known to serve as catalysts for epoxidation of simple olefins, the cationic Mn-salen complex is the most efficient. 

A unique titanium(IV)-silica catalyst prepared by impregnating silica with TiCLt or organotitanium compounds exhibits excellent properties with selectivities comparable to the best homogeneous molybdenum catalysts.285 The new zeolite-like catalyst titanium silicalite (TS-1) featuring isomorphous substitution of Si(IV) with Ti(IV) is a very efficient heterogeneous catalyst for selective oxidations with H2C>2.184,185 It exhibits remarkable activities and selectivities in epoxidation of simple olefins.188,304-306 Propylene, for instance, was epoxidized304 with 97% selectivity at 90% conversion at 40°C. Shape-selective epoxidation of 1- and 2-hexenes was observed with this system that failed to catalyze the transformation of cyclohexene.306 Surface peroxotitanate 13 is suggested to be the active spe-... 

Asymmetric Epoxidation. Asymmetric epoxidation of nonfunctionalized alkenes manifests a great synthetic challenge. The most successful method of asymmetric epoxidation, developed by Katsuki and Sharpless,332 employs a Ti(IV) alkoxide [usually Ti(OisoPr)4], an optically active dialkyl tartrate, and tert-BuOOH. This procedure, however, was designed to convert allylic alcohols to epoxy alcohols, and the hydroxyl group plays a decisive role in attaining high degree of enantiofa-cial selectivity.333,334 Without such function, the asymmetric epoxidation of simple olefins has been only moderately successful 335... 

These findings prompted the development of chiral metalloporphyrin-catalyzed epoxidation of simple olefins. 

The retarding effect of alcohols on the rate of epoxidation manifests itself in the observed autoretardation by the alcohol coproduct.428,434 446,447 The extent of autoretardation is related to the ratio of the equilibrium constants for the formation of catalyst-hydroperoxide and catalyst-alcohol complexes. This ratio will vary with the metal. In metal-catalyzed epoxidations with fe/T-butyl hydroperoxide, autoretardation by tert-butyl alcohol increased in the order W < Mo < Ti < V the rates of Mo- and W-catalyzed epoxidations were only slightly affected. Severe autoretardation by the alcohol coproduct was also observed in vanadium-catalyzed epoxidations.428 434 446 447 The formation of strong catalyst-alcohol complexes explains the better catalytic properties of vanadium compared to molybdenum for the epoxidation of allylic alcohols.429 430 452 On the other hand, molybdenum-catalyzed epoxidations of simple olefins proceed approximately 102 times faster than those catalyzed by vanadium.434 447 Thus, the facile vanadium-catalyzed epoxidation of allyl alcohol with tert-butyl hydroperoxide may involve transfer of an oxygen from coordinated hydroperoxide to the double bond of allyl alcohol which is coordinated to the same metal atom,430 namely,... 

Using the clear homology of epoxidation of olefin and the oxidation of sulfide, Jacobsen and co-workers65 and Katsuki and co-workers66,67 applied their system developed for the asymmetric epoxidation of simple olefin to the asymmetric oxidation of prochiral sulfides. 

The active species too is characterized by rather unusual properties and is different from soluble Ti-peroxides, known for their inertness in the epoxidation of simple olefins. As originally proposed by Clerici et al., the active sites contain Ti-OOH species, stabilized in a cyclic structure by the coadsorption of a protic molecule, generally the alcohol solvent. The oxygen transfer step to the double bond has electrophilic character thus resembling other peroxidic oxidants (Figure 15). 

The epoxidation of simple olefins which cannot benefit from secondary interactions brings some formidable problems that were solved by sophisticated catalyst design, mainly by the groups of Jacobsen and Katsuki in the 1990 s. A class of square planar salen complexes was chosen (Figure 19, for example) capable of giving a metal-oxo derivative by reaction with monooxygen donors such as iodosobenzene or sodium hypochlorite (the preferred oxidant). A series... 

Precursor of Useful Chiral Ligands. OPEN is widely used for the preparation of chiral ligands. Organometallic compounds with these ligands act as useful reagents or catalysts in asymmetric induction reactions such as dihydroxylation of olefins, transfer hydrogenation of ketones and imines, Diels-Alder and aldol reactions, desymmetrization of meso-diols to produce chiral oxazolidinones, epoxidation of simple olefins, benzylic hydroxylation, and borohydride reduction of ketones, imines, and a,p-unsaturated carboxylates. ... 

Periodate compounds have been used for the epoxidation of simple olefins too (MIO4, MH4O6, or M2H3IO6 M = Li, Na, K, Rb, Cs, etc.). In alkaline medium, xenon-trioxide epoxidizes alkenes stereoselectively there is no c/s-hydroxylation as when other inorganic oxides are employed. ... 

Ito, Y. N., Katsuki, T. Oxidation of the C C bond metal catalyzed epoxidation of simple olefins. Asymmetric Oxidation Reactions 2001,19-37. 

Some efforts were made in order to obtain good enantioselectivities in the epoxidation of simple olefins using methyltrioxorhenium (MTO), urea hydrogen peroxide (UHP) and six different chiral non racemic 2-substituted pyridine ligands, some of which are novel UHP was chosen as the hydrogen peroxide source in order to avoid unfavourable competition from water for vacant sites on the metal. However, poor enantioselectivity was reached (3-12% ee). 

R. Sinigaglia, R. A. Michelin, F. Pinna, G. Strukul, Asymmetric epoxidation of simple olefins catalyzaed by chiral diphosphine-modified Platinum(II) complexes", Organometallics 6 (1987) 728. 

Table 2. Epoxidation of simple olefins, allylic and homoallylic alcohols with aqueous H2O2 in the presence of the hydrophilic LDH-[W042, Cl ] ...

Scheme 8.6. Jacobsen s approach to epoxidation of simple olefins, fa) A few examples of (salen)Mn(III) epoxidation catalysts prior to reaction with NaOCl.

PlL = lPl(CF3)((2A,3A,)-chiraphos)(Cll2Cl2)]BF4 SCHEME 30. Asymmetric epoxidation of simple olefins. 

An alternative approach for the epoxidation of simple olefins has been developed by Pietikainen and co-workers and Katsuki and co-workers by using the Jacobsen-type catalysts (Fig. 23) and in situ addition of imidazole or N-methylimidazole (122,129). The highest cc-values obtained were 60 % for... 

Another interesting asymmetric catalyst for epoxidation of simple olefins such as cis-PhCH=CHMe was reported by Jacobsen and coworkers. In this example the catalyst was a chiral manganese salen-based complex (3.54) (Figure 3.22), and the oxidant used was NaOCl high yields and ee of > 90% were achieved. 

Methyltrioxorhenium (MTO) has perhaps been the most successful homogeneous catalyst for the epoxidation of simple olefins with hydrogen peroxide, however, attempts to modify the catalyst to achieve enantioselective epoxidation or anchoring to a solid support have met with only moderate success, probably because... 

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