Epoxidation Jacobsen

Although this is a resolution approach, racemic epoxides are readily available, and other than the catalysts, the substrate and water are the only materials present. 

The methodology, including the use of other nucleophiles, can be used to produce chiral compounds from meso-epoxides in high yield [137-139]. 

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Jacobsen epoxidation 359 -, Katsuki epoxidation 361 -, Mukaiyama-aldol reaction 367 f. -, oxime ether reduction 363 -, Sharpless asymmetric dihydroxyla-tion 361... 

Shi s method gives good results for disubstituted /f-alkenes compared to the Jacobsen epoxidation previously described, which is more specific for disubstituted Z-alkenes. Concerning the epoxidation of trisubstituted alkenes, the epoxidation of 1-phenyl-1-cyclohexene could not be validated because of... 

Soluble polymer-bound catalysts for epoxidation reactions have also been explored, with a complete study into the nature of the polymeric backbone performed by Janda [70]. Chiral (salen)-Mn complexes were appended to MeO-PEG, NCPS, Jan-daJeF and Merrifield resin via a glutarate spacer. It was found that for the Jacobsen epoxidation of ds-/ -mefhylstyrene, the enantioselectivities for each polymer-supported catalyst were comparable (86-90%) to commercially available Jacobsen catalyst (88%). Both soluble polymer-supported catalysts could be used twice before a decline in yield and enantioselectivity was observed. However, neither soluble polymer support proved as suitable as the insoluble JandaJel-supported (salen)-Mn complex for the epoxidation because residual impurities during precipitation and leaching of Mn from the complex, resulted in lowered yields. 

The Jacobsen Epoxidation allows the enantioselective formation of epoxides from various -substituted olefins by using a chiral Mn-salen catalyst and a stoichiometric oxidant such as bleach. 

Compared to the Sharpless Epoxidation, the Jacobsen Epoxidation allows a broader substrate scope for the transformation good substrates are conjugated c/s-olefins or alkyl-substituted cis-olefins bearing one bulky alkyl group. 

Jacobsen epoxidation of cyclohexa-1,4-dienes allowed a direct comparison of Mn (in)salen-catalysed epoxidation and C-H oxidation within the same molecule... 

Jacobsen epoxidation turned out to be the best large-scale method for preparing the cis-amino-indanol for the synthesis of Crixivan, This process is very much the cornerstone of the whole synthesis. During the development of the first laboratory route into a route usable on a very large scale, many methods were tried and the final choice fell on this relatively new type of asymmetric epoxidation. The Sharpless asymmetric epoxidation works only for allylic alcohols (Chapter 45) and so is no good here. The Sharpless asymmetric dihydroxylation works less well on ris-alkenes than on trans-alkenes, The Jacobsen epoxidation works best on cis-alkenes. The catalyst is the Mn(III) complex easily made from a chiral diamine and an aromatic salicylaldehyde (a 2-hydroxybenzaldehyde). 

The Sharpless asymmetric dihydroxylation works best for tram disubstituted alkenes, while the Jacobsen epoxidation works best for cis disubstituted alkenes. Even in this small area, there is a need for better and more general methods. Organic chemistry has a long way to go. 

The importance of the counter-ion has been recognized. The counter-ion influences the spin multiplicities and, potentially, the relative rates of the stereospecific concerted and stepwise non-concerted processes. The calculations indicate that the active manganese-oxo species in the Jacobsen epoxidation may either be a high-spin quintet or triplet, depending on the ligand. 

Epoxidation of alkenes with complex of a chiral salen ligand and manganese(III), 1.69 or 1.70, is known as Jacobsen epoxidation ... 

Asymmetric epoxidation The catalytic asymmetric epoxidation of alkenes has been the focus of many research efforts over the past two decades. The non-racemic epoxides are prepared either by enantioselective oxidation of a prochiral carbon-carbon double bond or by enantioselective alkylidenation of a prochiral C=0 bond (e.g. via a ylide, carbene or the Darzen reaction). The Sharpless asymmetric epoxidation (SAE) requires allylic alcohols. The Jacobsen epoxidation (using manganese-salen complex and NaOCl) works well with ds-alkenes and dioxirane method is good for some trans-alkenes (see Chapter 1, section 1.5.3). 

The synthesis of the tetrasubstituted dihydroquinoline portion of siomycin Di, which belongs to the thiostrepton family of peptide antibiotics, was achieved in the laboratory of K. Hashimoto. The Jacobsen epoxidation was utilized to introduce the epoxide enantioselectively at the C7-C8 position. The olefin was treated with 5 mol% of Jacobsen s manganese(lll)-salen complex (R =f-Bu) and 4% aqueous NaOCI solution in dichloromethane. To enhance the catalyst turnover, 50 mol% of 4-phenylpyridine-A/-oxide was added to the reaction mixture. The desired epoxide was obtained in 43% yield and with 91% ee. 

The catalytic asymmetric synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine was developed by J. Lee et al. using an intramolecular epoxide opening 5-exo-tet) followed by ring expansion. The acyclic c/s-epoxide substrate was prepared in good yield and in greater than 94% ee by the Jacobsen epoxidation from the corresponding (Z)-alkene. ... 

J.E. Lynch and co-workers reported the asymmetric total synthesis of the PDE IV inhibitor CDP840 in which they utilized the Jacobsen epoxidation to introduce the only stereocenter of the target. The triaryl (Z)-olefin substrate was epoxidized with significantly higher enantiomeric excess than the triaryl ( )-olefin. This finding was interpreted with Jacobsen s skewed side-on approach model. 

Strassner, T., Houk, K. N. Predictions of Geometries and Multiplicities of the Manganese-Oxo Intermediates in the Jacobsen Epoxidation. Org. Lett. 1999, 1,419-421. 

Ugly facts, unfortunately, sometimes invalidate a beautiful mechanism. The Jacobsen epoxidation sometimes proceeds with loss of configurational purity of acyclic alkenes. This feature of the reaction can be explained by invoking radicals. Homolysis of the Mn C bond in the manganaoxetane intermediate would give a Mn(III) 1,4-diradical complex, and attack of the alkyl radical on O with displacement of Mn(II) would give the epoxide and regenerate the catalyst. 

Although the Jacobsen epoxidation can be used to make the chiral epoxide, the number of steps to the precursor alleviates any advantages associated with this approach [33]. 

These may seem strange molecules to have a place in the new chiral pool but they were made on a vast scale by Merck in the synthesis of their HIV protease inhibitor crixivan (Indinavir). They both come from Jacobsen epoxidation of indene 283 (chapter 25) the anti-compound 285 by opening the epoxide 284 at the benzylic centre with azide ion.51... 

Applications of the AD to epoxide transformation propranolol and diltiazem Part V - Jacobsen Epoxidation Part VI - Desymmetrisation Reactions Opening anhydrides Opening epoxides... 

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