Sharpless epoxidation enantioselective

Fig. 3.35. Enantioselective Sharpless epoxidation of achiral primary allylic alcohols.

Sharpless epoxidation of alkenylsilanols.1 Allylic silanols also undergo highly enantioselective Sharpless epoxidation. This reaction furnishes simple epoxides such as styrene oxide in high optical purity. Thus reaction of fram-(3-lithiostyrene il) with ClSi(CH,)2H gives 2, which can be oxidized to the alkenylsilanol 3. ShaTp-less epoxidation of 3 gives the epoxide 4, which is converted to styrene epoxide 5 by cleavage with fluoride ion. The stereochemistry of epoxidation of 3 is similar to that of the corresponding allylic alcohol. 

Fig. 3.29. Enantioselective Sharpless epoxidation of achiral primary allyl alcohols. If the substrates are drawn as shown, the direction of the attack of the complexes derived for l-( + ) and d-(-)-DET can be remembered with the following mnemonic L, from lower face ...

The conversion of alkenes to epoxides is covered in most introductory organic chemistry texts, often exemplified by the use of m-chloroperoxybenzoic acid (MCPBA) as the epoxidizing reagent. Bradley et al. compared the enantioselective Sharpless epoxidation of geraniol with the classical MCPBA method, which gives a racemic product 21). Hoye and Jeffrey have illustrated a... 

H. C. Guo, X. Y. Shi, X. Wang, S. Z. Liu, M. Wang, Liquid-phase synthesis of chiral tartrate ligand library for enantioselective Sharpless epoxidation of allylic alcohols, /. Org. Chem. 69 (2004) 2042. 

The success of the enantioselective Sharpless epoxidation to a large extent depends on the configuration of the double bond of an available substrate. Shibasaki et al. developed an efficient method of stereospecific synthesis of exocychc double bonds using 1,4-hydrogenation of conjugated dienes catalyzed by an arene-Cr(CO)3 complex [43]. Allylic alcohol 31b [44,45], a substrate for Sharpless epoxidation, was obtained using this procedure. Alcohol... 

Naruta and coworkers developed a method for the synthesis of an an-thracyclinone tetracyclic moiety based on a Lewis acid-mediated tandem Michael-Diels-Alder reaction of acryloyl quinone with pentadienyltins [165]. Subsequent enantioselective Sharpless epoxidation led to an enantiopure intermediate that was converted into ll-deoxydaunomycinone [166]. In more recent work, they obtained enantiomerically pure 7,ll-deoxydaunomycinone (176) and its analogues by the above strategy using the enantiopure penta-dienyltin derivative 171 [167], which was obtained in six steps from racemic ester 167 [168] (Scheme 34). 

From a historical perspective, the Monsanto process for the preparation of (l.)-DOPA in 1974 laid the foundation stone for industrial enantioselective catalysis. Since then it has been joined by a number of other asymmetric methods, such as enantioselective Sharpless epoxidation (glycidol (ARCO) and disparlure (Baker)), and cyclopropanation (cilastatin (Merck, Sumitomo) and pyre-throids (Sumitomo)). Nevertheless, besides the enantioselective hydrogenation of an imine for the production of (S)-metolachlor(a herbicide from Syngenta), the Takasago process for the production of (-)-menthol remains since 1984 as the largest worldwide industrial application of homogeneous asymmetric catalysis. [124]... 

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. 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

The scope of metal-mediated asymmetric epoxidation of allylic alcohols was remarkably enhanced by a new titanium system introduced by Katsuki and Sharpless epoxidation of allylic alcohols using a titanium(IV) isopropoxide, dialkyl tartrate (DAT), and TBHP (TBHP = tert-butyl-hydroperoxide) proceeds with high enantioselectivity and good chemical yield, regardless of... 

The Sharpless epoxidation is a popular laboratory process that is both enantioselective and catalytic in nature. Not only does it employ inexpensive reagents and involve various important substrates (allylic alcohols) and products (epoxides) in organic synthesis, but it also demonstrates unusually wide applicability because of its insensitivity to many aspects of substrate structure. Selection of the proper chirality in the starting tartrate esters and proper geometry of the allylic alcohols allows one to establish both the chirality and relative configuration of the product (Fig. 4-1). 

Natural compounds are also applied as chiral ligands in enantioselective homogeneous metallo-catalysts. A classical example is the Sharpless epoxidation of primary allylic alcohols with tert-butyl hydroperoxide [37]. Here the diethyl ester of natural (R,R)-(+)-tartaric acid (a by-product of wine manufacture) is used as bi-dentate ligand of the Ti(iv) center. The enantiomeric excess is >90%. The addition of zeolite KA or NaA is essential [38], bringing about adsorption of traces of water and - by cation exchange - some ionization of the hydroperoxide. 

In this chapter, the ligand design for the catalytic enantioselective oxidations developed after the Katsuki-Sharpless epoxidation and the Sharpless AD will be discussed. 

Last year, a short enantioselective total synthesis of herbarumin III (42) in 11% overall yield was published the approach applied uses Keck s asymmetric allylation and Sharpless epoxidation to build the key fragment. Esterification with 5-hexenoic acid and a RCM was used to yield 42. Finally, another asymmetric synthesis of herbarumin III (42) was carried out using (R)-cyclohexylidene glyceraldehyde as the chiral template. The key steps of the synthesis were the enantioselective preparation of the... 

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. 

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