Indirect epoxidation

The formation of epoxides is synthetically a very important transformation. The indirect epoxidation of olefins (see Eq. 7) in the presence of electrogenerated chlorine (or bromine) [95] is a commercial process in which chlorine is recycled and not part of the product. The products such as propylene oxide are key intermediates in many further chemical processes. 

Peracid epoxidation and indirect epoxidation via the halohydrin route normally display opposite diastereoselectivity. In the indirect epoxidation route, the steric course is normally controlled by the first step, the formation of the most stable halonium ion, and not by the second step, the (tranx-diaxial) attack by the (nucleophilic) oxygen species. However, the relative rates and equilibria of both steps depend on the source of positive halogen and the reaction conditions which strongly influence the obtained stereoselectivity (Tables 3 and 4, and Section 4.5.1.1.3,). 

Scheme 18.28 Indirect epoxidation of cyclo-octene catalysed by aluminium salts.

Shimizu et al. have introduced an indirect route to stabilized lithiated epoxides. Treatment of dichlorohydrin 184 with 3 equiv. of vinyllithium in the presence of 3 equiv. of LTMP gave lithiated epoxide 185, which could be trapped with a range of electrophiles (e. g., Me3SnCl) to give 1,2-divinyl epoxides 186 these in turn underwent Cope rearrangements on heating to give oxepanes 187 (Scheme 5.43) [67]. 

Two recent reports described addition of nitrogen-centered nucleophiles in usefully protected fonn. Jacobsen reported that N-Boc-protected sulfonamides undergo poorly selective (salen) Co-catalyzed addition to racemic epoxides. However, by performing a one-pot, indirect kinetic resolution with water first (HKR, vide infra, Table 7.1) and then sulfonamide, it was possible to obtain highly enantiomer-ically enriched addition products (Scheme 7.39) [71]. These products were transformed into enantioenriched terminal aziridines in straightforward manner. 

When asymmetric epoxidation of a diene is not feasible, an indirect route based on asymmetric dihydroxylation can be employed. The alkene is converted into the corresponding syn-diol with high enantioselectivity, and the diol is subsequently transformed into the corresponding trans-epoxide in a high-yielding one-pot procedure (Scheme 9.5) [20]. No cpirricrizalion occurs, and the procedure has successfully been applied to natural product syntheses when direct epoxidation strategies have failed [21]. Alternative methods for conversion of vicinal diols into epoxides have also been reported [22, 23]. 

The reactivity of epoxides can be modified by various proximal functionality. For example, 2,3-epoxy sulfides 118 are converted to the corresponding TMS-thiiranium species 119 upon treatment with TMS triflate. This intermediate reacts with O-silyl amides regiospecifically to form l-substituted-3-hydroxy-2-thioethers (e.g., 120). Simple primary amines undergo polyalkylation, but imines can be used as an indirect amine equivalent <96TET3609>. 

Tumorigenicity of tetrahydroepoxides. As yet, only Ch H -epoxide has been directly demonstrated to be tumorigenic (18). However, indirect evidence has been found in the high tumorigenicity of 3,4-dihydro BA, 9,10-dihydro BeP and 3,4-dihydrobenz[c]acridine (19-21), each of which is a likely metabolic precursor of a bay-region H -epoxide. In the case of 9,10-dihydro BeP, cis- and trans-9,10-dihydroxy -9,10,11,12-tetrahydro BeP were identified as products of metabolism of 9,10-dihydro BeP (22), and are the expected products of hydration of the epoxide. Diols are also formed from 7,8-dihydro BaP upon metabolism with prostaglandin endoperoxide synthase (23) or with rat liver homogenates (24). 

Epoxidation of olefins Propylene -> Propylene oxide U.S., Europe, Japan - Indirect oxidation via BrO, or cio-... 

Access to P-mannosides [209] is illustrated by the preparation of 179 from P-glucoside 178 by oxidation of the equatorial 2-OH followed by stereoselective reduction to give the axial alcohol an efficient indirect route to the a-mannosides [206] utilizes the P-thioglucoside 182, readily obtained from epoxide 173, proceeding via an oxidation-reduction protection sequence to give P-thiomannoside glycosyl donor 184, from which a-mannoside 185 can be stereoselectively prepared. 

A method for preparing a Ti/Cr203 electrode has been developed for the indirect electrooxidation of 2-propanol to acetone [149]. Epoxidation of alkenes has been performed using oxo[5,10,15,20-tetrakis(2,6-dimethyl-3-sulfonatophenyl)... 

The natural glucocorticoid is hydrocortisone (cortisol). Semi-synthetic 9a-bromohydrocortisone 21-acetate was found to be less active as an anti-inflammatory agent than hydrocortisone 21-acetate by a factor of three, and 9a-iodohydrocortisone 21-acetate was also less active by a factor of 10. However, 9a-fluorohydrocortisone 21-acetate (fludrocortisone acetate) was discovered to be about 11 times more active than hydrocortisone acetate. Although the bromination sequence shown is equally applicable to chlorine and iodine compounds, fluorine must be introduced indirectly by the P-epoxide formed by base treatment of the 9a-bromo-lip-hydroxy analogue. 

These species, and in particular the Ti derivative, have a fundamental significance, being related to the Sharpless epoxidation reaction. In fact, despite the many attempts made in order to isolate and characterize the titanium tartrate peroxide derivative involved in that enantioselective process, only indirect evidence in solution and theoretical calculation clues have been obtained so far . ... 

In view of the efficient inhibition of a particular crystalline glycan hydrolase by the epoxylbutyl -cellobioside 7 (n = 2), we decided to prepare the deoxy iodo derivative 21 to aid in the X-ray crystallographic analysis. We soon found that, although the alkene 22 was easily available as a direct precursor to our target, the epoxide functionality had to be introduced indirectly using bromo-hydrin 23 technology any direct oxidation of 22 invariably led to some loss of the iodine atom [23]. 

The symmetrical oxepin oxide (105) has not to date been prepared by direct epoxidation of (7) but has been synthesized indirectly by the thermal gxtrusion of either carbon monoxide (74AG(e)672) or nitrogen (76JA6350) from appropriate precursors (Scheme 21). 

Indirect toxicity is not so apparent. It most often results from the biotransformation of what may appear to be a relatively unreactive molecule to a highly reactive intermediate, such as an epoxide or a radical species, through Phase 1 metabolism. Occasionally, a Phase 2 (conjugation) step is involved. 

If small amounts of PhSSPh were deliberately added from the beginning, the more positive reduction potential could be applied from the start. Indirect electrochemical eliminations were also performed in the case of 1,2-dihalides Ringopening reactions by the redox catalytic method were possible in the case of methylene cyclopropanes and epoxides... 

The indirect electron transfer sensitization reported earlier when biphenyl was present in dicyanoanthracene-sensitized epoxide openings also finds analogy in the sensitized oxygenation of a mixture of trans-stilbene and tetraphenylethylene, eq. 76 (233) ... 

Diels-AUer reactions. This diene can serve as a precursor to the highly oxygenated cyclohexane derivative shikimic acid (3), as shown in Scheme 1. Oxidative desilylation of the Diels-Alder adduct 2 could not be effected with peracids, but was effected by cis-dihydroxylation (Upjohn procedure, 7, 256-257) followed by p-elimination of (CH3)3SiOH with TsOH. Introduction of the 4a,5P diol system was effected indirectly from the 4a,5a-epoxide in several steps, since direct hydrolysis of the epoxide resulted in a mixture of three triols.1... 

It thus seems that there is no direct link between volumetric and elastic properties in the glassy state and that the anomalous density variations cannot be attributed to a crosslink density effect, either direct (on molecular packing) or indirect (through internal antiplasticization as discussed below). It seems reasonable to correlate this behavior with the presence of unreacted epoxides. The density would be (in the systems under consideration) a continuously increasing function of the amine/epoxide ratio, owing to the... 

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