Ethers asymmetric epoxidation

The oxidation of enol ethers and their derivatives is a useful method for the synthesis of a-hydroxy-ketones or their derivatives, which are versatile building blocks for organic synthesis. Since enol ethers and esters are types of olefin, some asymmetric epoxidation and dihydroxylation reactions have been applied to their oxidation. 

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

Diepoxidation of a diene Diepoxidation of the diene 1 with m-chloroper-benzoic acid gives a mixture of the d,l- and meso-diepoxides, whereas Sharpless epoxidation results in d- or 1-2 by a double asymmetric epoxidation. On treatment with base, 2 rearranges to the diepoxide a and then cyclizes to the meso-tetra-hydrofuran 3, a unit of teurilene, a cytotoxic C, -cyclic ether of red algae. This... 

Asymmetric epoxidation of 10a under standard conditions yields the crystalline epoxy alcohol 2a in 95% ee (91% chemical yield). Treatment of 9a with thioanisol in 0.5N NaOH, in rerf-butyl alcohol solution, gives -after protection of the hydroxyl groups as benzyl ethers- the sulfide a (60% overall yield) through an epoxide ringopening process involving a Payne rearrangement. Since the sulfide could not be hydrolysed to the aldehyde 7a without epimerisation at the a-position, it was acetoxylated in 71% yield under the conditions shown in the synthetic sequence (8a... 

Hori, K., Tamura, M., Tani, K., Nishiwaki, N., Ariga, M. and Tohda, Y. Asymmetric Epoxidation Catalyzed by Novel Azacrown Ether-type Chiral Quaternary Ammonium Salts under Phase-transfer Catalytic Conditions. Tetrahedron Lett. 2006, 47, 3115-3118. 

Asymmetric epoxidation catalyzed by novel azacrown ether-type chiral... 

ASYMMETRIC EPOXIDATION CATALYZED BY NOVEL AZACROWN ETHER-TYPE CHIRAL QUATERNARY AMMONIUM SALTS UNDER PHASE-TRANSFER CATALYTIC CONDITIONS... 

ASYMMETRIC EPOXIDATION OF (E)-CHALCONE CATALYZED BY THE AZACROWN ETHER-TYPE QUATERNARY AMMONIUM SALT AS CHIRAL PTC... 

The azacrown ether-type chiral quaternary ammonium salts as chiral PTCs are easily prepared from BINOL in four steps. Remarkably, Table 6.10 shows that the good efficiency of asymmetric epoxidation of various chalcones can be achieved by adjustment of the length of the carbon chains on the nitrogen atom in the quaternary ammonium salts. 

Table 6.10 Asymmetric epoxidation of chalcones catalyzed by the azacrown ether-type quaternary ammonium salts as Chiral PTCs (see Figure 6.8).

Asymmetric epoxidation of a,jS-unsaturated ketones represents an efficient method for the preparation of optically active a,jS-epoxy ketonesJ Recently, a new and very efficient catalytic system for enantioselective epoxidation of ( )-a,jS-enones to the corresponding trans-epoxy ketones has been developed based on a BlNOL-zinc complexJ Very high yields and excellent diastereo- and enantioselectivities are achieved at room temperature using cumene hydroperoxide (CMHP) as the terminal oxidant and performing the reaction in diethyl ether. A combination of enantio-merically pure BINOL and diethylzinc readily affords the active catalyst in situ (Figure 6.13). ... 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

The epoxy alcohol 47 is a squalene oxide analog that has been used to examine substrate specificity in enzymatic cyclizations by baker s yeast [85], The epoxy alcohol 48 provided an optically active intermediate used in the synthesis of 3,6-epoxyauraptene and marmine [86], and epoxy alcohol 49 served as an intermediate in the synthesis of the antibiotic virantmycin [87], In the synthesis of the three stilbene oxides 50, 51, and 52, the presence of an o-chloro group in the 2-phenyl ring resulted in a lower enantiomeric purity (70% ee) when compared with the analogs without this chlorine substituent [88a]. The very efficient (80% yield, 96% ee) formation of 52a by asymmetric epoxidation of the allylic alcohol precursor offers a synthetic entry to optically active 11 -deoxyanthracyclinones [88b], whereas epoxy alcohol 52b is one of several examples of asymmetric epoxidation used in the synthesis of brevitoxin precursors [88c]. Diastereomeric epoxy alcohols 54 and 55 are obtained in combined 90% yield (>95% ee each) from epoxidation of the racemic alcohol 53 [89], Diastereomeric epoxy alcohols, 57 and 58, also are obtained with high enantiomeric purity in the epoxidation of 56 [44]. The epoxy alcohol obtained from substrate 59 undergoes further intramolecular cyclization with stereospecific formation of the cyclic ether 60 [90]. 

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Scheme 8.6 Crown ether-catalyzed asymmetric epoxidation.

It should finally be pointed out that the mild reaction conditions typically employed in dioxirane-mediated oxidations enable the asymmetric epoxidation of enol ethers and enol esters. With the silyl ethers, work-up provides enantiomeri-cally enriched a-hydroxy ketones. As summarized in Table 10.1, quite significant enantiomeric excesses were achieved by use of catalyst 10 at loadings ranging from 30 [30] to 300 mol% [31]. Enol esters afford the intact acyloxyepoxides enantiomeric purities are, again, quite remarkable. 

Cavallo et al. from (+)-dihydrocarvone and evaluated in the asymmetric epoxida-tion of several silyl enol ethers [32]. Enantiomeric excess up to 74% was achieved in the epoxidation of the TBDMS trans-enol ether of desoxybenzoin with the fluoro ketone 19d (30 mol% of the ketone catalysts). In earlier work Solladie-Cavallo et al. had shown that the fluoro ketones 19a and 19e can be used to epoxidize trans-stilbene with up to 90% ee (30 mol% ketone catalyst) [33], Asymmetric epoxidation of trans-methyl 4-para-methoxycinnamate using ketone 19e as catalyst is discussed in Section 10.2. 

Acetonitrile is the solvent of choice for in-situ C-H oxidation. Although ethereal solvents, for example dimethoxymethane, 1,2-dimethoxyethane, 1,4-dioxane, and mixtures thereof, have been successfully used for dioxirane-mediated catalytic asymmetric epoxidations, their application in in-situ C-H oxidation has not been vigorously established. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

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