Epoxidation by mCPBA

In order to better understand the properties of the metathesized plant oils, postmodification of these polymerized seed oils was also examined [25]. To explore the possibilities of new materials that could arise from the polymerized oils, Larock and coworkers evaluated both the hydrogenation and epoxidation of metathesized soybean oils. Normally, thermally polymerized metathesized oils yield a yellow, brittle gel. This brittle gel is often undesirable, so other processes were investigated to develop a more usable material. In order to alter the properties of the material, complete hydrogenation was accomplished with 10% palladium on carbon to produce a white/pale cream-colored, crystalline material with melting points between 53 and 60 C. This metathesized soybean oil was also treated with conditions to invoke epoxidation of the double bonds. Unfortunately, the initial attempts with m-chloroperbenzoic acid (mCPBA) were problematic for the metathesized soybean oil despite being satisfactory for unaltered soybean oil. It was found that material that had been epoxidized by mCPBA would polymerize in a few hours, most likely due to the difficulty in the complete removal of the w-chlorobenzoic acid generated during the epoxidation. To circumvent this problem, conditions... 

The 1,2-carbonyl transposition takes place through the enJo-epoxide 18 easily prepared through the tosylhydrazone 16, followed by regioselective cleavage to the less substituted double bond (17) with 2 equivalents of methyllithium [4] and epoxidation with MCPBA in chloroform from the more accesible convex face of the decalin system. 

Different isomers of C qO have been prepared by photooxygenation [48], by MCPBA-oxidation [48], by ozonolysis [49] or they were extracted from fullerene soot [11, 50]. Isolation from fullerene soot and analysis of the product of photooxygenation and thermal ozonolysis yields only [6,6]-closed epoxide structures. As already observed for CgoO, ozonolysis and subsequent photolysis of the ozonide C7QO3 gives different [5,6]-open oxidoannulene structures [49]. 

Attempts to functionalize the homoallylic alcohol 15 quickly revealed that this product of an intramolecular aldol condensation was sensitive to base. Fortunately, heating with thiocarbonyldiimidazole effected clean dehydration to give predominantly the desired regioisomer of the diene. Methanolysis followed by oxidation then gave the triketone 1, which on epoxidation with MCPBA gave 2 as the minor component of a 3 1 mixture. 

The regioselectivity in the epoxidation of ethenylidenecyclopropanes by MCPBA strongly depends on the double-bond substituents. Thus, with alkyl substituents such as methyl 195, the adjacent electron-rich double bond is epoxidized, whereas the diphenyl analogue 196 reacts preferentially on the other double bond both primary products undergo subsequent rearrangements308. The MCPBA oxidation of the hindered cumulene 197 gave the cyclopropanones 198 and 199309. 

Initially, the products of these reactions suggested radical ions were involved138. In particular, when hexamethyl Dewar-benzene was epoxidized with MCPBA, the nature of the products depended on whether or not the iron(III) porphyrin hemin was added to the reaction mixture1381 . Furthermore, when Z-stilbene was epoxidized with dioxygen, catalyzed by (tetraphenylporphorinato)iron(III) chloride, -stilbene appeared in the reaction mixture139. 

Preparation of optically active P-ionone epoxide by a solid state kinetic resolution in the presence of the chiral host 10a is also possible. When a mixture of 10a, P-ionone (66) and m-chloroperbenzoic acid (MCPBA) is ground by mortar and pestle in the solid state, (+)-67 of 88% ee was obtained.29 Mechanism of the kinetic resolution is shown below. Of course, all processes proceed in the solid state. Firstly, oxidation of 66 with MCPBA gives rac-P-ionone epoxide (67). Secondly, enantioselective inclusion of (+)-67 with 10a occurs. Thirdly, uncomplexed (-)-67 is oxidized to give the Baeyer- Villiger oxidation product (-)-68 of 72% ee. This is the first example of the resolution by an enantioselective inclusion complexation in the solid state. 

The epoxide 6 is naturally electrophilic, but where does the epoxide come from By far the most important method of epoxide synthesis is the treatment of alkenes 19 with peroxy acids RCO3H 21. Alkenes are naturally nucleophilic 2 they react with bromine to give dibromides 20 and with electrophilic peroxyacids 21 to give epoxides. Again, these reactions convert nucleophilic alkenes into electrophilic derivatives. A very popular reagent for epoxidation is mCPBA (meta-chloro-perbenzoic acid) 21 R = 3-chlorophenyl but many other compounds are used. 

Fig. 7.10. Partial benzonitrile hydrolysis of (A) accelerated by hydrogen peroxide under basic conditions. The intermediate E, a perimidic acid, is as suitable for the epoxidation of standard alkenes as MCPBA or HHPP (cf. Section 3.19), but unlike the latter two is also capable of epoxidizing keto alkenes (which would be oxidized by MCPBA or MMPP in the ketonic substructure in a Baeyer-Vil-liger reaction cf. Section 14.35).

An orientation of addition that is the opposite of that predicted by the original statement of Markovnikov s rule one that gives the anti-Markovnikov product, (p. 334) (mefa-chloroperoxybenzoic acid) A common reagent for epoxidizing alkenes. MCPBA dissolves in common solvents such as dichloromethane. As the epoxidation takes place, the m-chlorobenzoic acid by-product precipitates out of solution, (p. 361)... 

C in dichloromethane. Solvent effects have been observed. Thus treatment of enol ether (53) with MCPBA in ether resulted in isolation of the benzoate (54). This was considoed to arise as a result of the increased nucleophilicity of the residual carboxylic acid in ether over that in dichloromethane. Isolation of the silyloxy epoxide by an analogous ethereal oxidation suggests periugrs that the 1,4-silyl migration is intrinsically less facile in this solvent. Generally however the process is efficiem and simple substrates are readily oxygenated (Scheme 11). 

Epoxidation. Precocene (1) causes larvae of certain insects to moult precociously to premature adults. The highly reactive epoxide 3, probably the active metabolite of 1, has now been synthesized. NBS oxidation of 1 in jiqueous THF affords bromohydrin 1, which when treated with NaH affords 3 in 88% yield. Attempts to prepare 3 by MCPBA, VOfacacfj-t-butylhydroperoxide, or Mo(CO) -f-butylhydroperoxide oxidations were unsuccessful. ... 

During the synthesis of such compounds, the epoxide is often installed at an early stage for example, dihydroquinoline 31 (Scheme 18) is readily epoxidized with MCPBA, and subsequent formation of the bis-alkynyl iodides followed by bis-intramolecular Stille coupling occurs with complete chemoselectivity <2006ARK261>. 

A recent application of the furan-carbonyl photocycloaddition involved the synthesis of the mycotoxin asteltoxin (147)." Scheme 16 shows the synthetic procedure that began with the photoaddition of 3,4-dimethylfuran and p-benzyloxypropanal to furnish photoaldol (148), which was epoxidized with MCPBA to afford the functionalized product (149) in 50% overall yield. Hydrolysis (THF, 3N HCl) provided the monocyclic hemiacetal which was protected as its hydrazone (150). Chelation-controlled addition of ethylmagnesium bromide to the latent a-hydroxy aldehyde (150) and acetonide formation produced compound (151), which was transformed through routine operations to aldehyde (152). Chelation-controlled addition of the lithium salt of pentadienyl sulfoxide (153) followed by double 2,3-sigma-tropic rearrangement provided (154) as a 3 1 mixture of isomers (Scheme 17). Acid-catalyzed cyclization of (154) (CSA/CH2CI2) gave the bicyclic acetal (155), which was transformed in several steps to ( )-asteltoxin (147). ... 

Relatively few arene dioxides and trioxides have been reported from PAHs. Arene dioxides in the naphthalene 152, 154, 155 and anthracene 157 series have been formed in good yield by direct epoxidation of the parent hydrocarbon. These arene dioxides 152, 154, 155, and 157 were formed by MCPBA epoxidation... 

The total synthesis of (+)-merrilactone A was accomplished by S.J. Danishefsky and co-workers. The last step of the sequence was an acid-induced homo-Payne rearrangement. The tetracyclic homoallylic alcohol precursor was first epoxidized using mCPBA. The epoxidation was expected to occur from the same face as the C7 hydroxyl group, but due to the congested nature of the C1-C2 double bond at its 3-face, the epoxide was formed predominantly on the a-face. The epoxide substrate then was exposed to p-toluenesulfonic acid at room temperature to afford the desired oxetane ring of the natural product. 

It is noteworthy that diethyl 1-(ethoxycarbonyl)methylphosphonate can be first metallated, then alkylated by an homoallyl iodide to give 4,5-unsaturated phosphonate, and further converted into epoxides by treatment with MCPBA in CH2CI2 in 93% yield. ... 

Now the time has come to react one of the alkenes and not the other. The reaction chosen was epoxidation as we could expect only the more nucleophilic non-conjugated alkene to be attacked by mCPBA. Direct epoxidation of the lactone 155 gave only the epoxide 164 with the correct chemoselectivity but the wrong stereoselectivity. The lactone bridge directs the peracid to the top face of the alkene. 

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