Diastereoselective epoxidation of chiral

SCHEME 6. Hydroxy-group directivity in the tftreo-diastereoselective epoxidation of chiral aUyhc alcohols by DMD... 

W. Adam, V. R. Stegmann, C. R. Saha-Moller, Regio- and Diastereoselective epoxidation of chiral allylic alcohols catalyzed by manganese(salen) and iron (porphyrin) complexes, J. Am. Chem. Soc. 121 (1999) 1879. 

Effect of the Oxidizing Agent and Catalyst Chirality on the Diastereoselective Epoxidation of... 

Chiral and achiral Jacobsen s catalysts exhibit similar diatereomeric excesses during the diastereoselective epoxidation of R-(+)-limonene using in situ prepared oxidizing agents. Therefore, the chiral center of the substrate appears to govern the chiral induction. In contrast, the chirality of the Jacobsen s catalyst appears to be responsible for the chiral induction when commercially available oxidants were used. 

As already mentioned, the dioxirane epoxidation of an alkene is a stereoselective process, which proceeds with complete retention of the original substrate configuration. The dioxirane epoxidation of chiral alkenes leads to diastereomeric epoxides, for which the diastereoselectivity depends on the alkene and on the dioxirane structure. A comparative study on the diastereoselectivity for the electrophihc epoxidants DMD versus mCPBA has revealed that DMD exhibits consistently a higher diastereoselectivity than mCPBA however, the difference is usually small. An exception is 3-hydroxycyclohexene, which displays a high cis selectivity for mCPBA, but is unselective for DMD . ... 

Diastereoselective reduction of chiral -keto sulfoxides (11,291-292). Chiral p-keto sulfoxides 1, prepared by reaction of p-(tolylsulfinyl)methyllithium with esters, are reduced by DIBAH in THF diastereoselectively to (R,S)-2. In the presence of ZnCl2, the opposite diastereoselectivity obtains. The paper includes a new method for conversion of these p-hydroxy sulfoxides into chiral epoxides.1... 

The epoxy-Ramberg-Backlund reaction (ERBR) has been used for the conversion of a,/3-epoxy sulfones into a range of mono-, di-, and tri-substituted allylic alcohols.34 Modification of this method has permitted the preparation of enantio-enriched allylic alcohols following the diastereoselective epoxidation of enantio-enriched vinyl sulfones that were accessed efficiently from the chiral pool. 

Finally, it should be mentioned that poly-amino acid catalysts have been used either to enhance or override substrate-induced diastereoselectivity in the Weitz-Scheffer epoxidation of chiral enones (Scheme 10.12) [90]. 

Fig. 3.38. Diastereoselective Sharpless epoxidation of chiral primary allylic alcohols (for the preparation of the substrate see Figure 17.63)...

Fig. 330. Diastereoselective Sharpless epoxidation of chiral primary allyl alcohols. (For preparation of starting materials, see Figure 14.54.)...

Ketone-catalyzed asymmetric and diastereoselective epoxidation of olefins by di-oxiranes generated in situ from chiral ketones and oxone (2KHS05 KH-S04 K2S04) 04ACR497. 

FIGURE 2.3 Diastereoselective epoxidation of a chiral terminal alkene with hydrogen peroxide catalyzed by 1b (2 mol%). 

W. Adam, T. Wirth, Hydroxy group directivity in the epoxidation of chiral allylic alcohols Control of diastereoselectivity through allylic strain and hydrogen bonding, Acc. Chem. Res. 32 (1999) 703. 

FIGURE 16.4 Effect of 1,2- and/or 1,3-allylic strain on the diastereoselectivity observed with sandwich polyoxometalate (POM)-catalyzed epoxidations of chiral allylic alcohols. 

Often, the diastereoselectivity may be attributed to the presence of one or more discrete functional groups, as in the epoxidation of chiral (E)-crotylsilanes which represents a key step for the asymmetric synthesis of substituted tetrahydrofurans (i. e., 35 37). Both catalyzed and uncatalyzed peracid oxidation conditions result in high anti selectivity, a phenomenon which is associated with the phenyldimethylsilyl and free hydroxyl groups. Epoxidation of the 0-protected species gives a 1 1 mixture of syn and anti isomers [94TL6453]. 

Chiral Auxiliary-hased Epoxidation of Substituted Alkenes. High diastereoselectivities were found for the m-CPBA or dimethyldioxirane epoxidation of chiral oxazolidine-substituted alkenes bearing a strongly basic urea group (eq 29). However, in most cases, the diastereoselectivities were superior with dimethyldioxirane. 

The epoxidation of chiral )9-alkoxy-Q , 3-unsaturated esters bearing a chiral auxiliary with m-CPBA led to a-hydroxy esters with high diastereoselectivities (eq 31). Both enantiomers are readily accessible simply by protecting the free hydroxy group on the auxiliary by a trimethylsilyl group (eq 32). 

As key intermediate for the introduction of chirality in positions 3 and 6 of 133, hydroxy-2,6,6-trimethylhex-2-en-l-one 19 was chosen this is readily available from the hydroxyketone (18) [24]. Reaction of 18 with mesyl chloride gave the corresponding mesylate which, on treatment with tetrabutylammonium acetate, was converted into the acetoxyketone 20 with complete inversion of configuration. The introduction of the second chiral centre was achieved by diastereoselective epoxidation of the protected hydroxyketone 27 with dimethyl sulphonium methylide, yielding the crystalline epoxide 22. This was readily transformed into the protected hydroxy-a-cyclocitral (23). Subsequent chain lengthening by a Horner-Emmons reaction gave a nitrile which, on treatment with MeLi, was converted into the crystalline C 13-hydroxy ketone 24 in excellent optical yield. The compounds mentioned were identified by m.p, [a] , IR, H-NMR, X-ray, CD and MS [24],... 

Besides stereoselective a-alkylation and Michael addition reactions, the epoxida-tion of a,p-unsaturated carlxMiyl acceptors using either hydrogen peroxide or hypochlorite as the oxygen source has emerged as a powerful methodology imder chiral phase-transfer cmiditimis. As an example for the potential of this methodology, the PTC-mediated stereoselective synthesis of loxistatin (88) was reported by Lygo et al. in 2006 [55], Herein, the diastereoselective epoxidation of enmie 89 has been employed as a key step in this sequence (Scheme 17). 

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