Sharpless epoxidation reaction

A model for the catalytically active species in the Sharpless epoxidation reaction is formulated as a dimer 3, where two titanium centers are linked by two chiral tartrate bridges. At each titanium center two isopropoxide groups of the original tetraisopropoxytitanium-(IV) have been replaced by the chiral tartrate ligand ... 

In order to obtain good yields, it is important to use dry solvent and reagents. The commercially available t-butyl hydroperoxide contains about 30% water for stabilization. For the use in a Sharpless epoxidation reaction the water has to be removed first. The effect of water present in the reaction mixture has for example been investigated by Sharpless et al. for the epoxidation of (E)-a-phenylcinnamyl alcohol, the addition of one equivalent of water led to a decrease in enantioselectivity from 99% e.e. to 48% e.e. 

In Sharpless epoxidation reactions, (Z)-substituted allylic alcohols react much more slowly than the corresponding (E )-substituted substrates, and sometimes the reaction is sensitive to the position of preexisting chirality in the selected substrate. For instance, in the presence of (+)-DET, chiral (E)-allylic alcohol 10 undergoes epoxidation in 15 hours to give product 11 as the major product with a diastereomeric ratio of >20 1. As for reaction with ( )-DET, 12 is then obtained, also with a diastereoselectivity of >20 1 (Scheme 4-4). 

Schreiber s model has also proved to be a general approach to a series of oxygenated metabolites of arachidonic acid, such as lipoxin A and lipoxin B.50 The family of linear oxygenated metabolites of arachidonic acid has been implicated in immediate hypersensitivity reactions, inflammation, and a number of other health problems. Among these metabolites, several compounds, such as lipoxin A, lipoxin B, 5,6-diHETE, and 14,15-diHETE possess 1-substituted (/ )-1 -alken-3.4-diol 84 as a common substructural moiety. Therefore, the car-binol 83 is an ideal substrate for generating compound 84 by applying Sharpless epoxidation reaction.50... 

Sharpless epoxidation reactions are thoroughly discussed in Chapter 4. This section shows how this reaction is used in the asymmetric synthesis of PG side chains. Kinetic resolution of the allylic secondary alcohol ( )-82 allows the preparation of (R)-82 at about 50% yield with over 99% ee (Scheme 7-23).19... 

Scheme 7-23. Kinetic resolution of the chiral co-side chain via Sharpless epoxidation reactions.

These species, and in particular the Ti derivative, have a fundamental significance, being related to the Sharpless epoxidation reaction. In fact, despite the many attempts made in order to isolate and characterize the titanium tartrate peroxide derivative involved in that enantioselective process, only indirect evidence in solution and theoretical calculation clues have been obtained so far . ... 

Even in the case of the Sharpless epoxidation reaction, where the stereochemical course has been confirmed in many examples, exceptions have been reported. As an illustration On enantioselective epoxidation in the presence of L-( + )-DIPT, meso-1,5-hcxadiene-3,4-diol (24a) gave epoxide 25 (formed in an unexpected mode) as the main product136 227 whereas, ( )-ben-zyl ether 24b, obtained from 24a by monobenzylation, on kinetic resolution in the presence of l.( + )-dipt yielded monoepoxide (+)-26, which belongs to the enantiomeric series (see also pp 420, 449 and 470) 37. 

T. Katsuki, V S. Martin, Asymmetric Epoxidation of Allylic Alcohols The Katsuki-Sharpless Epoxidation Reaction, Org. React. 1996, 48, 1-299. 

Asymmetric Epoxidation of Allylic Alcohols The Katsuki-Sharpless Epoxidation Reaction... 

Epoxidation. The last steps in a total synthesis of pentalenolactone (3) required epoxidation of 1, The reaction of alkaline hydrogen peroxide with 1 afforded mainly the undesired -epoxide, epimeric with 2. The desired reaction was effected by reduction of 1 with diisobutylaluminum hydride to the allylic hemiacetal and application of the Sharpless epoxidation reaction. After reoxidation (Jones reagent), the desired epoxide 2 was obtained in 45% yield. Alkaline hydrolysis then gave the natural product (3). ... 

Katsuki T, Martin VS. Asymmetric epoxidation of allylic alcohols the Katsuki-Sharpless epoxidation reaction. Org. Reactions 1996 48 1. 

We will see Sharpless epoxidation reactions in the Double Methods section towards the end of the chapter. Interestingly, Sharpless other famous asymmetric method - dihydroxylation - has not found widespread use in kinetic resolution. This is probably because the AD is just too powerful or, to be anthropomorphic, too wilful. In other words, it is not sensitive to the chirality of the substrate and charges ahead and reacts with both enantiomers. That is not to say there are not examples of kinetic resolution with dihydroxylation,19 but they are more rare. However, the dihydroxylation is even more useful and much more general than the kinetic resolution of allylic alcohols by asymmetric epoxidation and was discussed in Chapter 25. A slightly complicated case of kinetic resolution of alcohols by asymmetric dihydroxylation is in the Double Methods section. 

The polymer boxmd peroxocomplexes prepared in the present work have excellent catalytic potentiality and selectivity in the production of quinones. The chromium peroxocomplexes loses its activity on reaction and could be regenerated. The pwlymer bound vanadium catalyses sharpless epoxidation reactions. The high pore volume and a marginally good surface area shows that GMA-EGDM copolymers are good choice as supports. 

In Sharpless epoxidation reactions, the activity and enantioselectivity of the catalysis are significantly influenced by several variants, (i) Ti(0 Pr)4 is usually the choice of the titanium precursor, although the use of the corresponding tert-butoxide... 

A variety of a-heterosubstituted ketones and similar substrates are reduced by Sml2 under mild conditions, to form unsubstituted ketones. The heteroatom functionalities that can be re-ductively cleaved include halides (-1, -Br, -Cl), -SR, -S(0)R, -SO2R, and -OR (Molander and Hahn, 1986b Smith et al., 1988). Reductive cleavage of some of these heteroatom substituents requires the presence of HMPA as cosolvent for greater efficiency (Kusuda et al., 1989). a,f-Qpoxy ketones are also reduced to 0-hydroxy carbonyl compounds as shown in eq. (13) (Otsubo et al., 1987a). This is an important pathway for the synthesis of chiral f-hydroxy carbonyl compounds as the chiral substrates are easily synthesized by the sharpless epoxidation reactions. -epoxy esters require more vigorous conditions and the presence of HMPA for efficient reduction. 

A common strategy for building complexity from the products of Sharpless epoxidation reactions is to oxidize the alcohol to an aldehyde and add a nucleophile. Therefore asymmetric epoxidation reactions of a,p-unsaturated aldehydes would be a redox economical strategy [56] for the preparation of useful precursors. This strategy requires the use of nucleophilic oxidants since even the reactive variants of the Shi... 

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