Peroxide Induced Epoxidations

The reaction of peroxides with alkenes is probably the most common method for the preparation of epoxides (oxiranes). Peroxides are a source of electrophilic oxygen when they react with the nucleophilic n bond of an alkene. In Table 3.1, hydrogen peroxide (H2O2) was shown to be a powerful oxidizing agent, with a reduction potential of 1.77 Vl for the following reaction  

While most peroxide reactions involve homolytic cleavage of the O—O bond, generating free radicals (sec. 13.3), H2O2 and its monosubstituted derivatives can react with alkenes via either a concerted or ionic mechanism.244 Three categories of peroxides are used for epoxidation H2O2, alkyl hydroperoxides (155), 

The strength of the peroxide reagent correlates more or less with its reactivity with alkenes. In the following sections, the emphasis will be on the synthetic utility and generality of peroxide induced reactions. 

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Peroxyl radicals are the species that propagate autoxidation of the unsaturated fatty acid residues of phospholipids (50). In addition, peroxyl radicals are intermediates in the metabolism of certain drugs such as phenylbutazone (51). Epoxidation of BP-7,8-dihydrodiol has been detected during lipid peroxidation induced in rat liver microsomes by ascorbate or NADPH and during the peroxidatic oxidation of phenylbutazone (52,53). These findings suggest that peroxyl radical-mediated epoxidation of BP-7,8-dihydrodiol is general and may serve as the prototype for similar epoxidations of other olefins in a variety of biochemical systems. In addition, peroxyl radical-dependent epoxidation of BP-7,8-dihydrodiol exhibits the same stereochemistry as the arachidonic acid-stimulated epoxidation by ram seminal vesicle microsomes. This not only provides additional... 

Photochemically induced epoxidation of tetrafluoroethene by oxygen with improved yields (71-76%, conversion 21-62%) is achieved in the presence of radical generators such as tri-bromofluoromethane, 1,2-dibromotctrafluorocthane, ethyl nitrite or 1 H, /F,5//-octafluoropen-tyl nitrite.36 The oxidation of tetrafluoroethene with oxygen can also be catalyzed with bis(trifluoromethyl)diazene an undistillable viscous oil with peroxide composition is formed initially which can be quantitatively converted into carbonyl fluoride when heated.37-38... 

In the synthesis of aspyrone (994), an antibiotic isolated from the culture broth of Aspergillus species, lactaldehyde 990 supplies the asymmetric centers of the epoxide in the side chain (Scheme 134). The molecule is assembled convergently by addition of the lithium enolate of D-rhamnose-derived a-phenylseleno- -lactone 991 to aldehyde 990. After an initial aldol-type reaction, the intermediate alkoxide displaces tosylate to provide epoxide 992 with >99.8% stereoselectivity. Peroxide-induced elimination of phenylselenide furnishes TBS-protected aspyrone 993 in 61% overall yield from 990. 

Higher carboxylic acids such as acetic acid and propionic acid have also been used to epoxidize PBD [100]. Acetic acid is known not to react below 40°C with hydrogen peroxide to form a peracid therefore, a strong protraiic acid is added to catalyze peroxide formation [116]. Mineral acids such as sulfuric acid [117,118] or phosphoric acid [118] are effective for this. Trichloroacetic acid was found to induce epoxide opening faster than the epoxidation [118]. 

Because di-/ fZ-alkyl peroxides are less susceptible to radical-induced decompositions, they are safer and more efficient radical generators than primary or secondary dialkyl peroxides. They are the preferred dialkyl peroxides for generating free radicals for commercial appHcations. Without reactive substrates present, di-/ fZ-alkyl peroxides decompose to generate alcohols, ketones, hydrocarbons, and minor amounts of ethers, epoxides, and carbon monoxide. Photolysis of di-/ fZ-butyl peroxide generates / fZ-butoxy radicals at low temperatures (75), whereas thermolysis at high temperatures generates methyl radicals by P-scission (44). 

The second major discovery regarding the use of MTO as an epoxidation catalyst came in 1996, when Sharpless and coworkers reported on the use of substoichio-metric amounts of pyridine as a co-catalyst in the system [103]. A change of solvent from tert-butanol to dichloromethane and the introduction of 12 mol% of pyridine even allowed the synthesis of very sensitive epoxides with aqueous hydrogen peroxide as the terminal oxidant. A significant rate acceleration was also observed for the epoxidation reaction performed in the presence of pyridine. This discovery was the first example of an efficient MTO-based system for epoxidation under neutral to basic conditions. Under these conditions the detrimental acid-induced decomposition of the epoxide is effectively avoided. With this novel system, a variety of... 

A study of the anion-induced decomposition of 2-ethoxycarbonyl prop-2-enyl peroxides has established that epoxides so formed arise (Scheme 4) through (i) addition of the nucleophile to the acrylic unsaturated bond and (ii) intramolecular anionic... 

One mechanistic matter that has caused quite a bit of general consternation about a decade ago concerns the experimental evidence for the involvement of diradical intermediates (proposed as sources for the observed radical products) in dioxirane epoxidations, which were thought to be formed through induced peroxide-bond homolysis by the alkene. Nonetheless, rigorous experimental and high-level theoretical work disposed such radical chemistry in the epoxidation of alkenic substrates. The latter computations unequivocally confirm the established concerted mechanism, in which both CO single bonds in the incipient epoxide are concurrently formed by way of an asynchronous, spiro-structured transition state for the oxygen transfer. 

Sometimes, due to special conditions, chain transformation may hardly be induced. An example of this is the reaction of propylene epoxidation. However, intense generation of active sites (H02) in the primary reaction gives the possibility of suppressing acceptor chain transformation to undesired products and simultaneously stimulating the main direction—epoxidation. This is obtained due to chemical induction, which induces and speeds up selective transformation of propylene (acceptor) to a quite high rate. The authors have implemented such a conjugation mechanism in propylene epoxidation by hydrogen peroxide [10]. 

Berkessel A, Adrio JA (2004) Kinetic studies of olefin epoxidation with hydrogen peroxide in l,l,l,3,3,3-hexafluoro-2-propanol reveal a crucial catalytic role for solvent clusters. Adv Synth Catal 346 275-280 Berkessel A, Adrio JA (2006) Dramatic acceleration of olefin epoxidation in fluorinated alcohols activation of hydrogen peroxide by multiple H-bond networks. J Am Chem Soc 128 13412-13420 Berkessel A, Adrio JA, Huttenhain D, Neudorfl JM (2006a) Unveiling the booster effect of fluorinated alcohol solvents aggregation-induced conformational changes, and cooperatively enhanced H-bonding. J Am Chem Soc 128 8421-8426... 

Metals that are capable of 2e redox changes, typically main group elements and 4d and 5d transition metals, can give heterolysis of a peroxide to form a diamagnetic oxidant that may avoid the radical pathways seen in the case of equation (14-15). O atom transfer to the substrate is possible in this way. Sharpless epoxidation provides an excellent example. In this case rBuOOH is the primary oxidant, Ti(i-OPr)4 is the catalyst precursor and a tartrate ester is the ligand that induces a high ee in the epoxy alcohol formed from an allylic alcohol. This reaction has been successfiiUy developed on an industrial scale. 

H. Sugimoto, D. T. Sawyer, Ferric chloride induced activation of hydrogen peroxide for the epoxidation of alkenes and monoxygenation of organic substrates in acetonitrile, J. Org. Chem. 50 (1985) 1784. 

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