Asymmetric epoxidation conditions

The known allylic alcohol 9 derived from protected dimethyl tartrate is exposed to Sharpless asymmetric epoxidation conditions with (-)-diethyl D-tartrate. The reaction yields exclusively the anti epoxide 10 in 77 % yield. In contrast to the above mentioned epoxidation of the ribose derived allylic alcohol, in this case epoxidation of 9 with MCPBA at 0 °C resulted in a 65 35 mixture of syn/anti diastereomers. The Sharpless epoxidation of primary and secondary allylic alcohols discovered in 1980 is a powerful reagent-controlled reaction.12 The use of titanium(IV) tetraisopropoxide as catalyst, tert-butylhydro-peroxide as oxidant, and an enantiopure dialkyl tartrate as chiral auxiliary accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity. If the reaction is kept absolutely dry, catalytic amounts of the dialkyl tartrate(titanium)(IV) complex are sufficient. 

The efficiency of kinetic resolution is even greater when there is a silicon or iodo substituent in the (3 )-position of the C-1 chiral allylic alcohols. The compatibility of silyl substituents with asymmetric epoxidation conditions was first shown by the conversion of (3 )-3-trimethylsilylallyl alcohol into (2/ ,3/ )-3-trimethylsilyloxiranemethanol in 60% yield with >95% and further exploited by the conversion of ( )-3-(triphenylsilyl)-2-[2,3- H2]propenol into (2 ,3/ )-3-triphenylsilyl[2,3- H2]oxirane-methanol in 96% yield and with 94% gg.io7b,i07c. pentyl group at C-1, the k,A for asymmetric... 

Molybdenum and rhenium complexes have also been reported to promote the Baeyer-Villiger oxidation using O2. Although limited to cyclobutanones, Sharpless asymmetric epoxidation conditions have provided optically active lactones from hydroxymethylbutanone.35... 

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

The second method of asymmetric epoxidation has been extensively studied by Aggarwal et and is based on the reaction, under neutral conditions,... 

The second synthesis of crystalline 43 was reported by Mori as summarized in Scheme 62 [93]. The building block (4.R,5S)-A was prepared by an enzymatic process, while another building block C was synthesized via Sharpless asymmetric epoxidation. Coupling of A with C gave D, which was cyclized under Op-polzer s conditions to give crystalline E. When E was oxidized with Dess-Martin periodinane or tetra(n-propyl)ammonium perruthenate or Jones chromic acid, crystalline 43 was obtained. Swern oxidation or oxidation with 2,2,6,6-tetramethylpiperidin-1 -oxyl of E afforded only oily materials. Accordingly, oxidation of E to 43 must be executed extremely carefully. A synthesis of oily 43 was reported by Gil [94]. 

S. Arai, H. Tsuge, T. Shioiri, Asymmetric Epoxidation of a,p-Unsaturated Ketones under Phase-Transfer Catalyzed Conditions , Tetrahedron Lett. 1998,39,7563-7566. 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

If optimal conditions are desired for a specific asymmetric epoxidation.variation of the tartrate ester is likely to be a useful exercise. 

Asymmetric epoxidation of 10a under standard conditions yields the crystalline epoxy alcohol 2a in 95% ee (91% chemical yield). Treatment of 9a with thioanisol in 0.5N NaOH, in rerf-butyl alcohol solution, gives -after protection of the hydroxyl groups as benzyl ethers- the sulfide a (60% overall yield) through an epoxide ringopening process involving a Payne rearrangement. Since the sulfide could not be hydrolysed to the aldehyde 7a without epimerisation at the a-position, it was acetoxylated in 71% yield under the conditions shown in the synthetic sequence (8a... 

When a nonproteinogenic unsaturated amino acid was subjected to the Sharpless asymmetric epoxidation, 49 was formed (87TL3605). It is known that AAs are converted with phosgene into A-carboxy-a-amino acid anhydride (NCA) derivatives. Unexpectedly, A-protected dehydroaspartic acid gave l,3-oxazine-2,6-dione-4-carboxylic acid under such conditions (88CL1473). 

SCHEME 48. Catalytic asymmetric epoxidation of naphthoquinone derivatives under phase transfer catalyzed conditions... 

Previously, some fluorocyclohexanones were used in a catalytic amount with Oxone for asymmetric epoxidation reaction, but they gave a poor ee . It was found later that chiral ketones derived from fructose work well as asymmetric epoxidation catalysts and show high enantioselectivity in reactions of /rani-disubstituted and trisubsti-tuted olefins ". Cis and terminal olefins show low ee under these reaction conditions. Interestingly, the catalytic efficiency was enhanced dramatically upon raising the pH. Another asymmetric epoxidation was also reported using Oxone with keto bile acids. ... 

In 1980, Katsuki and Sharpless described the first really efficient asymmetric epoxidation of allylic alcohols with very high enantioselectivities (ee 90-95%), employing a combination of Ti(OPr-/)4-diethyl tartrate (DET) as chiral catalyst and TBHP as oxidant Stoichiometric conditions were originally described for this system, however the addition of molecular sieves (which trap water traces) to the reaction allows the epoxidation to proceed under catalytic conditions. The stereochemical course of the reaction may be predicted by the empirical rule shown in equations 40 and 41. With (—)-DET, the oxidant approaches the allylic alcohol from the top side of the plane, whereas the bottom side is open for the (-l-)-DET based reagent, giving rise to the opposite optically active epoxide. Various aspects of this reaction including the mechanism, theoretical investigations and synthetic applications of the epoxy alcohol products have been reviewed and details may be found in the specific literature . 

Hori, K., Tamura, M., Tani, K., Nishiwaki, N., Ariga, M. and Tohda, Y. Asymmetric Epoxidation Catalyzed by Novel Azacrown Ether-type Chiral Quaternary Ammonium Salts under Phase-transfer Catalytic Conditions. Tetrahedron Lett. 2006, 47, 3115-3118. 

ASYMMETRIC EPOXIDATION CATALYZED BY NOVEL AZACROWN ETHER-TYPE CHIRAL QUATERNARY AMMONIUM SALTS UNDER PHASE-TRANSFER CATALYTIC CONDITIONS... 

Asymmetric epoxidation of ailylic alcohols.1 Epoxidation of allylic alcohols with r-bulyl hydroperoxide in the presence of titanium(lV) isopropoxide as the metal catalyst and either diethyl D- or diethyl L-tartrate as the chiral ligand proceeds in > 90% stereoselectivity, which is independent of the substitution pattern of the allylic alcohol but dependent on the chirality of the tartrate. Suggested standard conditions are 2 equivalents of anhydrous r-butyl hydroperoxide with 1 equivalent each of the alcohol, the tartrate, and the titanium catalyst. Lesser amounts of the last two components can be used for epoxidation of reactive allylic alcohols, but it is important to use equivalent amounts of these two components. Chemical yields are in the range of 70-85%. 

This section presents a summary of the currently preferred conditions for performing Ti-catalyzed asymmetric epoxidations and is derived primarily from the detailed account of Gao et al. [4]. We wish to draw the reader s attention to several aspects of the terminology used here and throughout this chapter. The terms Ti-tartrate complex and Ti-tartrate catalyst are used interchangeably. The term stoichiometric reaction refers to the use of the Ti-tartrate complex in a stoichiometric ratio (100 mol %) relative to the substrate (allylic alcohol). The term catalytic reaction (or quantity) refers to the use of the Ti-tartrate complex in a catalytic ratio (usually 5-10 mol %) relative to the substrate,... 

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