Sharpless asymmetric epoxidation of allylic alcohol

The construction of key intermediate 18 can be conducted along similar lines. Sharpless asymmetric epoxidation of allylic alcohol 22 using (+)-DET furnishes epoxy alcohol 52b (Scheme 11). Subjection of the latter substance to the same six-step reaction sequence as that leading to 54a provides allylic alcohol 54b and sets the stage for a second SAE reaction. With (+)-DET as the... 

The MABR-promoted rearrangement, when applied to optically active epoxy substrates, has been shown to proceed with rigorous transfer of the epoxide chirality. Accordingly, used in combination with the Sharpless asymmetric epoxidation of allylic alcohols,5 this rearrangement represents a new approach to the synthesis of various... 

In connection with the synthetic work directed towards the total synthesis of polyene macrolide antibiotics -such as amphotericin B (i)- Sharpless and Masamune [1] on one hand, and Nicolaou and Uenishi on the other [2], have developed alternative methods for the enantioselective synthesis of 1,3-diols and, in general, 1, 3, 5...(2n + 1) polyols. One of these methods is based on the Sharpless asymmetric epoxidation of allylic alcohols [3] and regioselective reductive ring opening of epoxides by metal hydrides, such as Red-Al and DIBAL. The second method uses available monosaccharides from the "chiral pool" [4], such as D-glucose. 

Titanium-pillared montmorillonite may be used as a heterogeneous catalyst for the Sharpless asymmetric epoxidation of allylic alcohols (Scheme 20) (46). The enantiomeric purities of the epoxy products are comparable with those achieved using homogeneous Ti isopropoxide with molecular sieves as water scavengers (Chapter 4). Since basal spacing of the recovered catalyst after the reaction is unaltered, the catalyst can be recycled. 

Sharpless asymmetric epoxidation of allylic alcohols, asymmetric epoxidation of conjugated ketones, asymmetric sulfoxidations catalyzed, or mediated, by chiral titanium complexes, and allylic oxidations are the main classes of oxidation where asymmetric amplification effects have been discovered. The various references are listed in Table 4 with the maximum amplification index observed. 

Whereas these solid catalysts tolerate water to some extent, or even use aqueous H2O2 as the oxidant, the use of homogeneous Ti catalysts in epoxi-dation reactions often demands strictly anhydrous conditions. The homogeneous catalysts are often titanium alkoxides, possibly in combination with chiral modifiers, as in the Sharpless asymmetric epoxidation of allylic alcohols (15). There has recently been an increase in interest in supporting this enantioselective Ti catalyst. 

Table 4.11 Sharpless asymmetric epoxidation of allylic alcohols.a)...

Optically active allylic alcohols and homoallylic epoxides. The reaction of optically active 2,3-epoxy halides (1), available by Sharpless asymmetric epoxidation of allylic alcohols, with a preformed mixture of vinylmagncsium bromide and Cul (2 equiv. each) in THF at —23° does not result as expected (7.H1-82) in a homoallylic epoxide, but... 

A simple, divergent, asymmetric synthesis of the four stereoisomers of the 3-amino-2,3,6-trideoxy-L-hexose family was proposed by Dai and coworkers [222], which is based on the Katsuki-Sharpless asymmetric epoxidation of allylic alcohols (Scheme 13.115). Recently, A-trifluoroacetyl-L-daunosamine, A-trifluoroacetyl-L-acosamine, A-benzoyl-D-acosamine and A-benzoyl-D-nistosamine were derived from methyl sorbate via the methyl 4,5-epoxy-( -hex-2-enoates obtained via a chemoenzymatic method [223]. 

The Katsuki-Sharpless asymmetric epoxidation of ( )-allylic alcohols is the key-step in the total synthesis of all tetroses and hexoses developed by Sharpless and Masamune [259,260] and that are summarized in O Scheme 57 for the L-series. The epoxide obtained by oxidation of... 

Let s take these three chiral synthons in turn. First, the simplest one the central epoxide. The reagent we need here will carry a leaving group, such as a tosylate, and it can easily be made from the epoxy-alcohol. This gives a very good way of making this compound as a single enantiomer—a Sharpless asymmetric epoxidation of allyl alcohol, retrosynthetic analysis... 

The Sharpless asymmetric epoxidation of allyl alcohol gives the glycidol derivative 61 in 90% ee after in situ tosylation of 60 [63]. This process is working on a multiton-a-year scale (Arco Co., USA), facilitating the synthesis of a variety of /0-blockers. Asymmetric dihydroxylation of the allyl ether 63 catalyzed by a combined system of OSO4 and the cinchona alkaloid-based ligand 65 allows the commercial synthesis of the propranolol intermediate 64 in 91 % (Sepracor Co., USA) [64]. 

Epoxidations. Grafting tantalum onto silica to form a useful catalyst for the Sharpless asymmetric epoxidation of allyl alcohols is contrary to the ineffective titanium species on a similar support. Vanadium-complexed chiral hydroxamic... 

No discussion on catalytic asymmetric synthesis would be complete without mention of the Sharpless asymmetric epoxidation of allylic alcohols [34]. This utilises a Ti(IV)-tartrate catalyst and /-butyl hydroperoxide as the oxidant. High enantioselectivity can be achieved using this system for a wide variety of allylic alcohols. Commercial applications, however, are at present limited to relatively small scale production. 

The Sharpless asymmetric epoxidation of allylic alcohols (one of the reactions that helped K. Barry Sharpless earn his part of the 2001 Nobel Prize) offers a good example of an enantioselective technique that can be used to create either enantiomer of an epoxide product. This reaction uses a diester of tartaric acid, such as diethyl tartrate (DET) or diisopropyl tartrate (DIPT), as the source of chirality. The dialkyl tartrate coordinates with the titanium tetraisopropoxide [Ti(Oi-Pr)4] catalyst and t-butyl hydroperoxide (r-BuOOH) to make a chiral oxidizing agent. Since both enantiomers of tartaric acid are commercially available, and each enantiomer will direct the reaction to a different prochiral face of the alkene, both enantiomers of an epoxide can be synthesized. 

Oxiranecarboxylic acids 41 (glycidic acids) can be converted into a,P epoxy diazomethyl ketones 42 via mixed anhydrides. It was found that photolysis of these compounds in the presence of alcohols gave yhyunsaturated esters 44. It is thought that nucleophilic attack of the alcohol on the ketene 43 results in epoxide ring opening. The E olefin isomer is predominately formed, although small quantities of Z esters are also isolated (< 10%). Conveniently non-racemic, chiral substrates are readily prepared via Sharpless asymmetric epoxidation of allylic alcohol 39, followed by... 

SCHEME 34.1. (A) Sharpless asymmetric epoxidation of allylic alcohols 1 mediated by Ti(IV)-diethyltartrate (DET) catalyst with alkyl hydroperoxide as terminal oxidant leading to enantioenriched epoxides 2. (B) Preferential attack of the oxygen atom as a function of the stereochemistry of the DET chiral ligand. (C) Schematic representation of the dimeric active catalytic species 3. 

General experimental procedure for Sharpless asymmetric epoxidation of allylic alcohols A mixture of 4-A molecular sieves (15-20 wt% based on substrate) and CH2CI2 (40 mL) under nitrogen was cooled to —5°C. DET or DIPT (2 mmol) was added, followed by Ti(0(-Pr)4 (Immol). After cooling to —20°C, tert-butyl hydroperoxide (6.06 M in CH2CI2, 5mL, 30 mmol) was added, and the mixture was stirred for 10 minutes. AUyhc alcohol (20 mmol) in CH2CI2 (3 mL) was added dropwise. After stirring for 1 hour at —15°C to —5°C, water (6 mL) was added. The mixture was stirred for 30 minutes and allowed to warm to room... 

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