Sharpless reaction

Sharpless reaction of 47 occurred almost regioselectively to give the 2-(278, 60%), together with the 1-p-toluenesulfonamido derivatives (279,... 

Sharpless reaction of the enantiomeric alkenes (47) produced the precursors for 2-amino-2-deoxy-o -D and -L-carba-glucopyranoses. These compounds were converted into the penta-7V,0-acetates by the following sequence. Replacement of the bromo group with an acetate ion, treatment with sodium in liquid ammonia, and peracetylation. 

Like the vanadium-based epoxidation reaction, the Sharpless reaction in-... 

The 4 A Molecular Sieves System. The initial procedure for the Sharpless reaction required a stoichiometric amount of the tartrate Ti complex promoter. In the presence of 4 A molecular sieves, the asymmetric reaction can be achieved with a catalytic amount of titanium tetraisopropoxide and DET (Table 4-2).15 This can be explained by the fact that the molecular sieves may remove the co-existing water in the reaction system and thus avoid catalyst deactivation. Similar results may be observed in kinetic resolution (Table 4-3).15... 

Three divinyl carbinol substrates have been chosen as examples. They are good substrates for examination because the vinyl carbinols are known to undergo Sharpless reaction at low reaction rates. The results presented in Table 4-7 clearly show that the ee of 79 improves as the reaction proceeds toward completion. Note that the minor enantiomer 78 can be removed through a second, faster epoxidation that converts enantiomer 78 into an easily destroyed bis-epoxide 80 (Scheme 4-29 and Table 4-7). The same trend is apparent in the second demonstration with diisopropenyl carbinol 81 (Scheme 4-30 and Table 4-8). Similarly, the third reaction is the reaction of (E,E)-divinyl carbinol 82 (Scheme 4-31 and Table 4-9). 

Scheme 7-15 shows the significant improvement in overall stereoselectivity, due mainly to the adoption of the newly developed Sharpless asymmetric ep-oxidation. Compounds a-epoxy-67 and //-epoxy-67 can be readily obtained from 53 via the Sharpless reaction. Isomers of compounds 57 are then constructed via regioselective ring opening with a copper reagent. 

The Nobel Prize in Chemistry 2001 was awarded to three researchers for their pioneering work in the field of asymmetric catalysis. One of them, K. Barry Sharpless, was honored for the epoxidations named after him (Section 3.4.6). The second reason for the award was his development of the asymmetric dihydroxylation (AD Figure 17.21). The Sharpless reactions that were honored with the Nobel Prize have three things in common first, they are oxidations, second, they are catalytic asymmetric syntheses, and third, they owe their high enan-tiocontrol to the additive control of stereoselectivity. In the introductory passages to... 

Asymmetric Epoxidation of Allylic Alcohols The Sharpless Reaction"... 

There are many synthetic applications of epoxide formation. Titanium alkoxides in the presence of diethyltartrate as a chiral ligand catalyze the epoxidation of allylic alcohols enantioselectively (Sharpless reaction). In the presence of singlet... 

For example, starting from the synthetic ( )-isomer of natural combretastatin A-4 chiral hydroxylation (Sharpless) reactions produced the R,R) and (5, 5, )-diols (56 and 57, Scheme 14) which were evaluated against a series of cancer cell lines, and tubulin [35]. The dihydroxylation protocol was applied also to Combretastatin A-4 [17]. 

Enantioselective Epoxidation of Allylic Alcohols (Sharpless Reaction). . 69... 

Although some outstanding results have been obtained, there are some limitations to the scope of this process (see examples in Table 8.2). The reaction works best with cw-olefins, in contrast to the situation with the Sharpless reaction. This can be accommodated with a side-on approach of reagent to the catalyst system, as depicted... 

Using titanium(IV) tetraisopropoxide, fcrf-butyl hydroperoxide, and an enantiomerically pure dialkyl tartrate, the Sharpless reaction (Figure 2.7) accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity. 

Hb = "H, via a Sharpless reaction and found that the trianion 117 of hippuric acid would react with these to give products which, on deprotection, gave (2RS, 3R, 4R)- and (2RS, 3S, 4S)-[3,4- H2]homoserine lactones 112a, = H,... 

There can be no doubt that the reliability of the Sharpless reaction amongst many different classes of allyl alcohol contributes to its success as a synthetic tool in asymmetric synthesis. Another remarkable attribute of the Sharpless asymmetric epoxidation is the very high level of discrimination between enantiomers of secondary allylic alcohols leading to the wide use of this system for the kinetic resolution of these substrates. The kinetic resolution (Figure 4.5) was first reported using stoichiometric amounts of titanium/tartrate, but catalytic amounts of titanium may also be employed. ... 

Oxyamination of olefinic sugars using the Sharpless reaction (TSNHCI-OSO4) has been widely studied as a route to amino-sugars. Compounds of the general... 

Synthetic highlights The partial synthesis of paclitaxel was necessary to enhance the availability of the drug substance and avoid unsustainable use of yew trees. Many different synthetic routes have been reported and three inventive pathways for the enantioselective or site-selective approaches to various segments of the paclitaxel molecule are described. These are aU promoted by organometal catalytic complexes. Reactions presented include use of the intramolecular Heck reaction in the synthetic pathway to baccatine III the Sharpless reaction and the introduction of a trifunctional catalyst for biomimetic synthesis of chiral diols synthesis of the paclitaxel side-chain and use of a Zr-complex catalyst in the reductive N-deacylation of taxanes to primary amine, the key precursor of paclitaxel. 

Titanium alkoxides appear particularly useful catalysts as they can be highly stereospecific when associated to a chiral ligand such as L(+)-diethyltartrate (Sharpless reaction). 

This principle also operates very satisfactorily in oxidation reactions as the well-known and widely used Sharpless reaction clearly demonstrates. 

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