Epoxides substrates

The reaction between an aldehyde and a carbon nucleophile, such as a sulfur ylide, constitutes an alternative approach to the synthesis of epoxides. Since alkenes, which are the normal epoxidation substrates, are often formed from aldehydes, this approach can be highly efficient. On the other hand, the synthesis of appropriate carbon nucleophiles usually requires additional steps. 

By comparing interfacial inactivation rates in a stirred-cell (low and controlled area of exchange) and an emulsion system (high interfacial area), these authors have shown that the use of an emulsion system can be exploited to obtain high solute interphase mass-transfer rates since the rate of specific interfacial inactivation remains low. However, in this system, the presence of an epoxide substrate at high concentration in the organic phase increases the rate of interfacial inactivation. Addition of a sacrificial protein to the system, which can prevent adsorption of the catalytic enzyme at the interface, could provide a method to reduce the rate of interfacial inactivation. 

One especially interesting kinetic resolution/ asymmetric epoxidation substrate is (R,S)-2,4-hexadien-3-ol (80) [77]. The racemic diene has eight different olefinic faces at which epoxidation can occur and thereby presents an interesting challenge to the selectivity of the epoxidation catalyst. The selectivity can be tested by using slightly less than 0.5 equiv. of oxidant (because the substrate is a racemate, the maximum yield of any one product is 50%). When the reaction was run under these conditions, the only product that was formed was the (l/f,2/f,3/f)-epoxy alcohol 81. 

Coates and coworkers have carried out kinetic studies of the alternating copolymerization of CHO and C02 catalyzed by several of the P-diiminate zinc derivatives [29]. These authors have proposed a bimetallic mechanism to be operative, which is consistent with their experimental observations, including the large differences in activity noted for a series of structurally closely related catalysts. It was proposed that one zinc center would coordinate and activate the epoxide substrate, while the second zinc center would provide the propagating carbonate species to ring-open the epoxide. This proposal is represented by the transition state depicted in Figure 8.3a. 

The finding that the use of LDA as bulk base results in non-enantioselective deprotonation indicated that bulk bases which are much less reactive toward the epoxide substrate compared with the chiral lithium amide are needed. But they should be strong enough to regenerate the chiral amide from the amine formed in the epoxide rearrangement. 

The catalytic asymmetric synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine was developed by J. Lee et al. using an intramolecular epoxide opening 5-exo-tet) followed by ring expansion. The acyclic c/s-epoxide substrate was prepared in good yield and in greater than 94% ee by the Jacobsen epoxidation from the corresponding (Z)-alkene. ... 

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. 

The metabolism of the herbicide antagonist, trldlphane, by a GST system from corn is one of the few examples of the conversion of an epoxide substrate to a GSH conjugate by a plant system (99) (Equation 23). Based on chromatographic data, it appeared that this conversion also occurs in Intact com. 

Tetrakis(l,T-binaphthyl-2,2 -diyl phosphate) complexes (119) are reported to be much more effective catalysts than the more commonly used carboxylate complexes for enantioselective intramolecular, tandem, carbonyl ylide forma-tion/cycloaddition of a-diazo- -keto esters. The ring-opening reactions of epoxides with diphenyl phosphorazidate (120) have been investigated. A wide range of epoxide substrates have been studied and the products, (121) or (122), depend on the substrate structure. The microbial hydroxylation of novel phos-... 

The synthesis of cyclic carbonates in RTILs, via cycloaddition of cathodically activated carbon dioxide to epoxide, has been reported by Deng et al. [139]. Ionic liquids, saturated with CO by bubbling at normal pressure and containing the epoxidic substrate, were electrolyzed in an undivided cell (Cu as cathode. Mg or Al as sacrificial anode). The electrolyses were carried out under potentiostatic conditions at a potential negative enough to the selective reduction of CO to CO (E=-2.4 V vs. 

The Co(salen) catalyst is remarkably insensitive to the steric properties of terminal epoxide substrates, as substituents ranging from methyl to cyclohexyl to ferf-butyl groups are accommodated in the kinetic resolution. Propylene oxide presented an impressive illustration of catalyst enantiocontrol, where a kj i exceeding 400 was estimated for this substrate. This epoxide served to further emphasize the synthetic utiHty of this process, as the HKR of 1 mole of propylene oxide proceeded efficiently with catalyst that had been recycled from previous kinetic resolutions (Scheme 18) The HKR of propylene oxide has also been effected on a multi-hundred kilogram scale in the pilot plant at ChiRex. 

When we applied the above search strategy to various other meso-epoxide substrates, a number of important observations were made [14]. One significant trend that emerged from these studies was that for each epoxide substrate, as de-... 

The partitioning behavior of the epoxide (substrate) and the diol (product) between the two phases was first investigated. As a result, both the epoxide and the diol were mostly dissolved in the organic phase when chloroform, dodecanol, or /r-decane was used. Moreover, dodecanol and n-decane easily formed emulsions with the buffer (potassium phosphate or KPB), which were difficult to separate. When using n-hexane, n-octane, or isooctane as the organic solvent, the epoxide partitioned mainly in the organic phase while the diol dissolved mainly in the aqueous phase. The partition difference... 

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