Chiral epoxides, enantioselective asymmetric

Mechanistic studies103 revealed that chiral ketone-mediated asymmetric epoxidation of hydroxyl alkenes is highly pH dependent. Lower enantioselectivity is obtained at lower pH values at high pH, epoxidation mediated by chiral ketone out-competes the racemic epoxidation, leading to higher enantioselectivity. (For another mechanistic study on ketone-mediated epoxidation of C=C bonds, see Miaskiewicz and Smith.104)... 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

Recently, Shi and coworkers reported high enantioselective asymmetric epoxidation of a,/ -unsaturated esters by using the chiral ketone 35 as a catalyst and Oxone as an oxidant (equation 47) . ... 

A sequence of allylation, epoxidation and an acid-mediated 6-exo cyclisation converts salicylaldehydes into 2-hydroxymethyl-2-methyl-27/-[l]benzopyrans. A bicyclic chroman arising from attack of the hydroxymethyl group on the intermediate benzylic cation has been isolated <02SL322>. A twelve-step enantioselective synthesis of a 2-hydroxymethyl-2-methylchroman with an overall yield of 48% uses related methodology and introduces the chirality through an asymmetric Sharpless epoxidation <02JCS(P1)496>. 

The first enantioselective total synthesis of (- -)-l 1,12-epoxycembrene C (28) has been accomplished via a macro-olefination strategy by employing titanium-mediated McMurry coupling as a key step and the Sharpless asymmetric epoxidation for the introduction of chiral epoxide. Based on the enantioselective Sharpless asymmetric epoxidation, Li et al. assumed the configuration of natural 28 to be (115,125) (Scheme 6-21). ... 

Sharpless asymmetric epoxidation ° is an enantioselective epoxidation of an allylic alcohol with ferf-butyl hydroperoxide (f-BuOOH), titanium tetraisopropoxide [Ti(0-fPr)4] and (-b)- or (—)-diethyl tartrate [(-b)- or (—)-DET] to produce optically active epoxide from achiral allylic alcohol. The reaction is diastereoselective for a-substituted allylic alcohols. Formation of chiral epoxides is an important step in the synthesis of natural products because epoxides can be easily converted into diols and ethers. 

Chiral Ligand for Asymmetric Catalysis. Dimethyl l-tartrate is a demonstrated chiral ligand for the Ti -catalyzed asymmetric epoxidation of allylic alcohols (Sharpless epoxidation), and the Zn -mediated asymmetric cyclo-propanation of allylic alcohols (Simmons-Smith reaction), see lodomethylzinc Iodide Enantioselectivities in these reactions... 

In this context it is worth noting that neither the titanium(IV) tartrate catalyst nor other metal catalyst-alkyl hydroperoxide reagents are effective for the asymmetric epoxidation of unfunctionalized olefins. The only system that affords high enantioselectivities with unfunctionalized olefins is the manganese(III) chiral Schiff s base complex/NaOCl combination developed by Jacobsen [42]. There is still a definite need, therefore, for the development of an efficient chiral catalyst for asymmetric epoxidation of unfunctionalized olefins with alkyl hydroperoxides or hydrogen peroxide. 

Chiral epoxides frequently play a key role as intermediates in organic synthesis and the development of methods for the catalytic asymmetric synthesis of such compounds therefore remains an area of intensive research. Methods have focused principally on the asymmetric electrophilic oxidation of alkenes and good enantioselectivity has been achieved [1]. An alternative to oxidative processes for the synthesis of epoxides is the reaction of sulfur ylides with aldehydes and ketones [2,3,4,5,6]. Sulfur ylide epoxidation is a carbon-carbon bond forming reaction and is complementary to oxidative methods. The standard conditions for this reaction utilize the original Corey method treatment of a sulfonium salt with a strong base in the presence of or followed by the addition of an aldehyde... 

Epoxides in Asymmetric Synthesis Enantioselective Opening by Nucleophiles Promoted by Chiral Transition Metal Complexes... 

Reversal of enantioselectivity in Cu-chiral bipyridine-catalyzed asymmetric ring-opening reactions of meso-epoxides with indole and aniline derivatives is observed compared to Sc-chiral bipyridine-catalyzed reactions, where the same chiral ligand is used (Scheme 32). " It was revealed from X-ray crystal structural analysis that a square pyramidal structure for the Cu° complex and a pentagonal bipyramidal... 

It was found that 4-substitnted a,a-diarylprolinol 162 catalyzed the asymmetric epoxidation of a, 3-enones to give the corresponding chiral epoxides in good yields and high enantioselectivities (np to 96%) nnder mild reaction conditions (Scheme 1.68) [109]. The extension of epoxidation to cyclic ot,P-unsaturated ketones with chiral primary salts was reported by Wang et al. in good yields and excellent enantioselectivities (up to 99%) [110]. 

Diols may be prepared using 0s04-catalyzed processes or via epoxides. Sharpless asymmetric dihydroxylation and enantioselective epoxidations allow the preparation of chiral diols. 

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