Asymmetric epoxidation catalyst preparation

Chiral porphyrins, prepared in different ways84,85 (chiral units attached to preformed porphyrins84, chiral substituents introduced during the synthesis of porphyrins86 or chiral porphyrins synthesized without the introduction of chiral groups69,87-90), proved to be effective as asymmetric epoxidation catalysts. 

In 1996, Shi et al. [75] developed a fructose-derived ketone (Epoxone ) 183 as a highly effective asymmetric epoxidation catalyst. Shi s epoxidation is known to be the best for the asymmetric epoxidation of tramolefms and tri-substituted olefins. Shi s ketone is readily available and an efficient and selective oxidant that requires mild conditions. Ketone 183 could be synthesized [88] from inexpensive chiral starting material D-fructose, by ketalization and oxidation (Scheme 9.48). The enantiomer of 183 can be synthesized from L-fructose, which in turn could be obtained from commereially available L-sorbose. Chemists at DSM developed a scalable process for the preparation of Epoxone 183 in large quanities. 

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. ... 

Spectacular achievements in catalytic asymmetric epoxidation of olefins using chiral Mnm-salen complexes have stimulated a great deal of interest in designing polymeric analogs of these complexes and in their use as recyclable chiral catalysts. Techniques of copolymerization of appropriate functional monomers have been utilized to prepare these polymers, and both organic and inorganic polymers have been used as the carriers to immobilize these metal complexes.103... 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Aggarwal et al.108 reported excellent results with the catalytic asymmetric epoxidation of aldehydes. As shown in Scheme 4-52, a series of thioacetals 137 was prepared from hydroxy thiol 136 and the corresponding carbonyl compound. Among them, compound 138, derived from 136 and acetaldehyde, proved to be the best catalyst for asymmetric epoxidation of aldehydes. 

The product of this preparation is the most enantioselective catalyst developed to date for asymmetric epoxidation of a broad range of unfunctionalized olefins.6 The procedure includes a highly efficient resolution of trans-1,2-diaminocyclohexane as well as a convenient analytical method for the determination of its enantiomeric purity. This method is general for the analysis of chiral 1,2-diamines. The Duff formylation described in Step B is a highly effective method for the preparation of 3,5-di-tert-... 

Different approaches have been used in the preparation of heterogeneous Sharpless-type catalytic systems for the asymmetric epoxidation of allylic alcohols, although in most cases the chiral induction was modest (50-60%). Li and coworkers described the preparation of an organic-inorganic hybrid chiral catalyst grafted onto the surface of silica and in mesopores of MCM-41, and its successful application in asymmetric epoxidation . Enantiomeric excesses were higher than 80% with conversions in the range 22-76%. 

Although the parent formaldehyde-derived dioxirane (H2CO2) was the first of this intriguing class of cyclic peroxides to be prepared and spectrally characterized in 1976, the conversion of aldehydes into the corresponding dioxiranes by treatment with Caroate was deemed difficult because of the expectedly facile Baeyer-Villiger oxidation of the aldehydes to their carboxylic acids. Most gratifyingly, however, is that it was recently demonstrated that optically active aldehydes may also serve as promising catalysts for asymmetric epoxidations. For example, ee values up to 94% were obtained with the aldehyde 14 as dioxirane precursor. 

Asymmetric epoxidation of a,jS-unsaturated ketones represents an efficient method for the preparation of optically active a,jS-epoxy ketonesJ Recently, a new and very efficient catalytic system for enantioselective epoxidation of ( )-a,jS-enones to the corresponding trans-epoxy ketones has been developed based on a BlNOL-zinc complexJ Very high yields and excellent diastereo- and enantioselectivities are achieved at room temperature using cumene hydroperoxide (CMHP) as the terminal oxidant and performing the reaction in diethyl ether. A combination of enantio-merically pure BINOL and diethylzinc readily affords the active catalyst in situ (Figure 6.13). ... 

High epoxy alcohols such as 12 are prepared by Sharpless asymmetric epoxidation. Kohji Suda of Meiji Pharmaceutical University, Tokyo, has described (J.. Am. Chem. Soc. 2004,126,9554) the optimization of Cr TPP as a catalyst for the rearrrangement of the epoxides such as 12 to the corresponding aldehyde. The reaction proceeds without loss of . 

Finally, a titanium(IV) pillared clay (Ti-PILC) catalyst has been prepared.71 In the presence of tartaric acid esters as chiral ligands Ti-PILC is an effective, heterogeneous catalyst for the asymmetric epoxidation of allylic alcohols. Enantioselectivities were comparable to those observed in the homogeneous system - and reactions could be carried out at concentrations up to 2M with a simple work-up via filtration of the catalyst. 

Ti(IV) isopropoxide [Chemical Abstracts nomenclature 2-propanol, Ti(4+) salt], is the Ti species of choice for preparation of the Ti-tartrate complex in the asymmetric epoxidation process. The use of Ti(IV) f-butoxide has been recommended for reactions in which the epoxy alcohol product is particularly sensitive to ring opening by the alkoxide [18]. The 2-substituted epoxy alcohols are one such class of compounds. Ring opening by f-butoxide is much slower than by i-propoxide. With the reduced amount of catalyst that now is sufficient for all asymmetric epoxidations, the use of Ti(0-f-Bu)4 appears to be unnecessary in most cases, but the concept is worth noting. 

Several factors contribute to the frequent use of (3 )-substituted allylic alcohols (13) for asymmetric epoxidation (a) The allylic alcohols are easily prepared (b) conversion to epoxy alcohol normally proceeds with good chemical yield and with better than 95% ee (c) a large variety of functionality in the (3E) position is tolerated by the epoxidation catalyst. Representative epoxy alcohols (14) are summarized in Table 6A.4 [2,4,18,41-53] and Figure 6A.3 (4,54-61], with results divided arbitrarily according to whether the (3E) substituent is a hydrocarbon (Table 6A.4) or otherwise (Fig. 6A.3). The versatility of these and other 3-substi-tuted epoxy alcohols for organic synthesis is illustrated with several examples in the following discussion. 

Asymmetric epoxidation of allylic alcohols is a very reliable chemical reaction. More than a decade of experience has confirmed that the Ti-tartrate catalyst is extremely tolerantof structural diversity in the allylic alcohol substrate for epoxidation yet is highly selective in its ability to discriminate between the enantiofaces of the prochiral olefin. Today the practitioner of organic chemistry need provide only the allylic alcohol to perform the reaction. All other reagents and materials required for the reaction are available from supply houses and usually are sufficiently pure as received to be used directly in the asymmetric epoxidation process. [When purchasing f-butyl hydroperoxide in prepared solutions, however, the more concentrated 5.5-M solution in isooctane (2,2,4-trimethylpentane) should always be chosen over the 3.0-M solution.] If the considerations presented in this chapter are observed, with attention to the moderately stringent technique outlined, no difficulty should be encountered in performing this reaction. 

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