Trans epoxides

Note that is must be the trans olefin as it is the trans epoxide we want. Tins is all right as the Wittig reaction can easily be controlled to give mostl the more stable trans olefin. 

Only the trans epoxide is chiral As formed in this reaction neither product is optically active... 

A concerted [2 + 2] cycloaddition pathway in which an oxametallocycle intermediate is generated upon reaction of the substrate olefin with the Mn(V)oxo salen complex 8 has also been proposed (Scheme 1.4.5). Indeed, early computational calculations coupled with initial results from radical clock experiments supported the notion.More recently, however, experimental and computational evidence dismissing the oxametallocycle as a viable intermediate have emerged. In addition, epoxidation of highly substituted olefins in the presence of an axial ligand would require a seven-coordinate Mn(salen) intermediate, which, in turn, would incur severe steric interactions. " The presence of an oxametallocycle intermediate would also require an extra bond breaking and bond making step to rationalize the observation of trans-epoxides from dy-olefms (Scheme 1.4.5). 

Historieally, the epoxidation of trans-olefins typieally affords trans-epoxides with low enantioseleetivity. In 1991, Jaeobsen reported that trans-epoxides ean be obtained... 

Table 1.4.2. Epoxidation of cis-olefins to give trans-epoxides...

Although trans epoxides ean be obtained via epoxidation of aeyelie cti-eonjugated olefins under speeified eonditions, a direet method based on the epoxidation of trans-olefins would be valuable. The Katsuki group reeently identified eatalyst 15 as an effieient catalyst for the direet epoxidation of trans-olefins. Crucial to the sueeess of the eatalyst is the inherent adoption of a deeply folded eonformation eoupled with the use of ehlorobenzene as solvent. While only a limited number of substrates have been examined to date using catalyst 15, the results are very promising. For example, trans- -methyl styrene is epoxidized in 91% ee, trans-P-n-butyl styrene in 95% ee, and trans-stilbene in 87% ee. 

To a solution of m-ethyl cinnamate (44, 352 mg, 85% pure, 1.70 mmol) and 4-phenylpyridine-A-oxide (85.5 mg, 29 mol%) in 1,2-dichloromethane (4.0 mL) was added catalyst 12 (38.0 mg, 3.5 mol%). The resulting brown solution was cooled to 4°C and then combined with 4.0 mL (8.9 mmol) of pre-cooled bleach solution. The two-phase mixture was stirred for 12 h at 4°C. The reaction mixture was diluted with methyl-t-butyl ether (40 mL) and the organic phase separated, washed with water (2 x 40 mL), brine (40 mL), and then dried over Na2S04. The drying agent was removed by filtration the mother liquors concentrated under reduce pressure. The resulting residue was purified by flash chromatography (silica gel, pet ether/ether = 87 13 v/v) to afford a fraction enriched in cis-epoxide (45, cis/trans . 96 4, 215 mg) and a fraction enriched in trans-epoxide cis/trans 13 87, 54 mg). The combined yield of pure epoxides was 83%. ee of the cis-epoxide was determined to be 92% and the trans-epoxide to be 65%. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

Quinidine, a natural product epimeric with quinine at Cg and C9, was accessed through the diastereoisomeric trans epoxide prepared from 86 by SAD, in this case by using AD-mix a [2b, 41]. 

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]. 

In the condensation reaction between chloro- and bromo-methyl aryl sulfones and carbonyl compounds, a-sulfonyloxiranes were obtained. In this condensation reaction, bases such as potassium t-butoxides372, NaH373 and aqueous concentrated hydroxide with benzyltriethylammonium chloride under two-phase condensation were used374. In the reaction with aldehydes only the trans-epoxide isomers resulted, whereas lith-iofluoromethyl phenyl sulfone 289375 and 291376 were found to add to aldehydes affording /J-hydroxysulfones 290 and 292, respectively. 

The mesoporous character of MCM-41 overcomes the size limitations imposed by the use of zeolites and it is possible to prepare the complex by refluxing the chiral ligand in the presence of Mn +-exchanged Al-MCM-41 [34-36]. However, this method only gives 10% of Mn in the form of the complex, as shown by elemental analysis, and good results are only possible due to the very low catalytic activity of the uncomplexed Mn sites. The immobihzed catalyst was used in the epoxidation of (Z)-stilbene with iodosylbenzene and this led to a mixture of cis (meso) and trans (chiral) epoxides. Enantioselectivity in the trans epoxides was up to 70%, which is close to the value obtained in solution (78% ee). However, this value was much lower when (E)-stilbene was used (25% ee). As occurred with other immobilized catalysts, reuse of the catalyst led to a significant loss in activity and, to a greater extent, in enantioselectivity. 

The epoxidation of electon-defident olefins using a nucleophilic oxidant such as an alkyl hydroperoxide is generally nonstereospecific epoxidation of both cis- and /nmv- ,/3-unsatii rated ketones gives the trans-epoxide preferentially. However, the epoxidation of cis-ofi-unsaturated ketones catalyzed by Yb-(40) gives civ-epoxides preferentially, with high enantioselectivity, because the oxidation occurs in the coordination sphere of the ytterbium ion (Scheme 26).132... 

In contrast to the epoxidation of a,/3-unsaturated ketones, the metal-catalyzed asymmetric epoxidations of o,/3-unsaturated esters are much more limited in number. Epoxidation of ethyl m-cinnamatc with Mn(salen) (26) has been reported to give a mixture of the corresponding cis-(93% ee) and trans-epoxides in a ratio of 4 1.133... 

Five- and six-membered cyclic allenylidenesiloxanes have been prepared by internal displacements of siloxane epoxides by lithiated propargylic siloxanes (Eqs. 9.49-9.51) [58], The mode of attack is related to the stereochemistry of the epoxide. A trans epoxide (Eq. 9.49) give rise to a six-membered siloxane by a 6-endo pathway, whereas cis epoxides (Eqs. 9.50 and 9.51) undergo 5-exo cleavage. 

Asymmetric monoepoxidation of conjugated dienes has been accomplished via (salen)Mn(III)-catalyzed [salen = A,Ar/-bis(salicylidene)ethylenediamine] oxidation. The reaction exhibits regioselectivity for attack at cis double bonds of cA.traws-conjugated dienes, and affords trans epoxides as the major products from cis olefins33. Thus, diene 14 gave optically active fraws-vinylepoxide 15 as the major product with 87% ee as shown in equation 16. 

The epoxidation of alkenes is one of the most impoi4ant oxidation methods. Electrochemical epoxidation of electron-poor olefins such as enoates (154 155) and enones has been accomplished by using silver(III)oxo bis(2,2 -bipyridine) and similar complexes (Scheme 61) [241], )-Dimethyl glutaconate is electrolyzed in an MeCN-LiCl04/Ag0Ac)(bpy)-(Pt) system to give the trans-epoxide in 90% yield. 

Crotti and co-workers work on regiochemical control of ring opening of epoxides by means of chelating agents has continued. Under standard conditions the regio-isomeric C(l) derivatives are the sole products from the trans epoxides (22a) and (22b) and are the predominant products from the cis epoxides (23a) and (23b). Under chelating conditions the cis epoxides unexpectedly show a consistent increase in C(2) selectivity. The results are discussed in terms of electronic and steric effects. 

Oxygen transfer via radical intermediate (tran -epoxide) ... 

Scheme 31. Reaction for AlECR of trans epoxides with anilines as nucleophiles using the catalysts 67-69.

Temp. °C Time (min). MW(W) Trans-epoxide Ee(%) Yield(%) Anti-/ -amino Alcohols Yield(%) Ee(%) ... 

As stoich. [Ru(0)(bpy)(tmtacn)]VCH3CN it functioned as a competent (sic) epoxidant for alkenes, though the products were often contaminated with by-products (e.g. fran -stilbene gave fran -stilbene oxide and benzaldehyde cw-stilbene gave cis- and trans- epoxides). Kinetics of the epoxidation of norbomene and styrene were reported, with activation parameters measured and discussed [682]. Kinetics of its non-stereospecific, stoicheiometric epoxidation of aromatic alkenes in CH3CN were studied, and the rates compared with those of oxidations effected by other Ru(IV) 0x0 complexes with N-donors, e. g. [Ru(0)(tmeda)(tpy)] ", trans-[Ru(0)(Cl3bpy)(tpy)] " and [Ru(0)Cl(bpy)(ppz )] + [676]. 

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