Epoxidation with enantiomeric conversion

The Jacobsen-Katsuki-catalysts (Fig. 13) have recently received much attention as the most widely used alkene epoxidation catalysts. An example of Jacobsen s manganese-salen catalyst is shown in Fig. 13. They promote the stereoselective conversion of prochiral olefins to chiral epoxides with enantiomeric excesses regularly better than 90% and sometimes exceeding 98%.82,89,92,93,128 The oxidation state of the metal changes during the catalytic cycle as shown in Scheme 8. 

In order to assess whether intramolecular cooperativity could occur within the dendrimeric [Co(salen)]catalyst the HKR of racemic l-cyclohexyl-l,2-ethenoxide was studied at low catalyst concentrations (2xl0 " M). Under these conditions the monomeric [Co(salen)] complex showed no conversion at all, while the dendritic [G2]-[Co(salen)]catalyst gave an impressive enantiomeric excess of 98% ee of the epoxide at 50% conversion. Further catalytic studies for the HKR with 1,2-hexen-oxide revealed that the dendritic catalysts are significantly more active than a dimeric model compound. However, the [Gl]-complex represents already the maximum (100%) in relative rate per Go-salen unit, which was lower for higher generations [G2] (66%) and [G3] (45%). 

Kinetic resolution of chiral aUylic alcohols.7 Partial (at least 60% conversion) asymmetric epoxidation can be used for kinetic resolution of chiral allylic alcohols, particularly of secondary allylic alcohols in which chirality resides at the carbinol carbon such as 1, drawn in accordance with the usual enantioface selection rule (Scheme I). (S)-l undergoes asymmetric epoxidation with L-diisopropyl tartrate (DIPT) 104 times faster than (R)-l. The optical purity of the recovered allylic alcohol after kinetic resolution carried to 60% conversion is often > 90%. In theory, any degree of enantiomeric purity is attainable by use of higher conversions. Secondary allylic alcohols generally conform to the reactivity pattern of 1 the (Z)-allylic alcohols are less satisfactory substrates, particularly those substituted at the /1-vinyl position by a bulky substituent. 

Several years later, the group of Corma reported on a successful study on stereoselective olefin epoxidation with MTO using various chiral nitrogen bases. Although the conversion is low (10%), an enantiomeric excess (ee) of up to 36% can be obtained with cA-p-methylstyrene as the substrate and R-(+)-1 -phenylethylamine as base (Fig. 3b) [34], Also, the groups of Saladino and Crucianelli used /f-(+)- -phenylethylamine as chiral base in a 1 1 ratio with MTO, forming the corresponding perrhenate salt, but also here, very low conversion is obtained. In the same report, the use of Lrans-( R,2R)-, 2-diaminocyclohexane (Fig. 3c) in combination with MTO as... 

Molander also showed that enantiomerically enriched a,(1-epoxy ketones, such as 42, prepared by Sharpless asymmetric epoxidation underwent efficient conversion to enantiomerically enriched (1-hydroxy ketones 43 upon treatment with Sml2 (Scheme 4.27).31... 

A number of new oxaziridinium epoxidation reagents have been reported. A new axially chiral epoxidation catalyst 4 has been reported <070BC501>. These catalysts, as are others, are converted to an oxaziridinium with Oxone, which then epoxidizes the olefin. This study examined several chiral groups on the nitrogen as well as both atropisomers. The (S,F)-isomer 4 provided the (1R,2R) epoxide with moderate enantioselectivity and 82% conversion. The (.V,A/)-isomcr of 4 provided the (lS,2S)-epoxide in slightly lower enantiomeric excess (76%) and lower conversion as well. 

The use of inorganic supramolecular compounds in catalysis has also been successful in recent years. Hupp etal. incorporated a Mn(IIl)-porphyrm (see Porphyrin) epoxidation catalyst inside a molecular square, a system that shows enhanced catalyst stabihty and substrate selectivity as compared to the free catalyst. In another example, chiral metaUocyclophanes were constructed from Pt(PEt3)2 units and enantiopme atropoisomeric t,t -binapthyl-6,6 -bis-(acetylenes) and used in enantioselective diethyl zinc addition to aldehydes to afford chiral secondary alcohols. The first organometaUic triangle based on Pt(II) and alkyne-di-substituted-binaphfhyl system was reported and found to effect asymmetric catalysis reactions of aldehydes to alcohols with excellent conversion rates and enantiomeric excess/ ... 

Complete conversions and good enantiomeric excesses (64-100%) were achieved in the asymmetric epoxidation of chromenes and indene using UHP as oxidant and a novel dimeric homochiral Mn(III) Schiff base as catalyst. The reactions were carried out in the presence of carboxylate salts and nitrogen and oxygen coordinating co-catalysts. However, the epoxidation of styrene unfortunately proceeded with incomplete conversion and only 23% ee. Modification of the catalyst and use of pyridine 7V-oxide as cocatalyst allowed improvement of the ee to 61% (Scheme 18). ... 

Double kinetic resolution. Davies et at.2 have noted that the enantiomeric selectivity of Sharplcss asymmetric epoxidation of an allylic alcohol can be enhanced in some cases by use of two kinetic resolutions. Thus epoxidation of the allylic alcohol 1 with (+)-DiPT as the chiral component (58% conversion) provides the epoxide 2 and the less reactive enantiomer (R) of I, which can be recovered and epoxidized with (—)-DiPT. Using this technique, the epoxide 3 was obtained from I in 86% ec. This strategy is... 

The conversion of the chromene 54 to epoxide 55 (a synthetic precursor for potassium channel modulators) and diol 56 (Fig. 40) may be achieved by a number of microbial catalysts, notably Mortierella rammaniana SC 13840 which gives the diol 56 in 65% yield m. 91% optical purity [62]. In an analogous conversion, the related microorganism Mortierella isabellina ATCC 42613 converted both chromenes 57 and 58 (Fig. 41) to a mixture of the corresponding cis- and tran -diols, presumably the result of regio- but nonstereo-selective acid-catalyzed hydrolysis of an intermediate epoxide, with both isomeric diols being formed in identical enantiomeric purities [34]. 

A new stereoselective epoxidation catalyst based on a novel chiral sulfonato-salen manganese(III) complex intercalated in Zn/Al LDH was used successfully by Bhattacharjee et al. [125]. The catalyst gave high conversion, selectivity, and enantiomeric excess in the oxidation of (i )-limonene using elevated pressures of molecular oxygen. Details of the catalytic activities with other alkenes using both molecular oxygen and other oxidants have also been reported [126]. 

Different approaches have been used in the preparation of heterogeneous Sharpless-type catalytic systems for the asymmetric epoxidation of allylic alcohols, although in most cases the chiral induction was modest (50-60%). Li and coworkers described the preparation of an organic-inorganic hybrid chiral catalyst grafted onto the surface of silica and in mesopores of MCM-41, and its successful application in asymmetric epoxidation . Enantiomeric excesses were higher than 80% with conversions in the range 22-76%. 

The preparation of the allene bis-epoxide 1 started with isovaleraldehyde 9. Addition of the protected propargyl alcohol 10 under the Carreira conditions led to 11 in > 95% . Mesylation followed by displacement with methyl cuprate provided the allene without loss of enantiomeric excess. Oxidation of the allene 12 with dimethyldioxirane could have led to any of the four diastereomers of the spiro bis epoxide. In the event, only two diastereomers were observed, as a 3 1 mixture. That 1 was the major diastereomer followed from its conversion to 3. The configuration of the minor diastereromer was not noted. Exposure of 1 to nucleophilic azide then gave the easily-purified 2. 

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