Allylic enantioselective epoxidation

Figure 6.4 Some successful examples of kinetic resolution of allylic alcohols by enantioselective epoxidation [21, 27].

Ordinary alkenes (without an allylic OH group) have been enantioselectively epoxidized with sodium hypochlorite (commercial bleach) and an optically active manganese-complex catalyst. Variations of this oxidation use a manganese-salen complex with various oxidizing agents, in what is called the Jacobsen-Katsuki... 

The enantioselective epoxidation method developed by Sharpless and co-workers is an important asymmetric transformation known today. This method involves the epoxidation of allylic alcohols with fcrt-butyl hydroperoxide and titanium (sopropoxide in the presence of optically active pure tartarate esters, see Eqn. (25). 

The use of alkylhydroperoxides as epoxidizing agents for allylic alcohols under catalytic conditions was soon expanded into enantioselective epoxidation with use of the more mild titanium alkoxides in the presence of chiral tartaric esters116. As concerns the epoxidation of functionalized dienes, these now so-called Sharpless conditions [Ti(OPr )4, dialkyl tartrate, TBHP] have been utilized to enantioselectively epoxidize 1,4-pentadiene-... 

Although the Sharpless catalyst was extremely useful and efficient for allylic alcohols, the results with ordinary alkenes were very poor. Therefore the search for catalysts that would be enantioselective for non-alcoholic substrates continued. In 1990, the groups of Jacobsen and Katsuki reported on the enantioselective epoxidation of simple alkenes both using catalysts based on chiral manganese salen complexes [8,9], Since then the use of chiral salen complexes has been explored in a large number of reactions, which all utilise the Lewis acid character or the capacity of oxene, nitrene, or carbene transfer of the salen complexes (for a review see [10]). 

Enantioselective epoxidation of allylic alcohols using t-butyl peroxide, titanium tetra-wo-propoxide, and optically pure diethyl tartrate. 

This method has proven to be an extremely useful means of synthesizing enantiomerically enriched compounds. Various improvements in the methods for carrying out the Sharpless oxidation have been developed.48 The reaction can be done with catalytic amounts of titanium isopropoxide and the tartrate ester.49 This procedure uses molecular sieves to sequester water, which has a deleterious effect on both the rate and enantioselectivity of the reaction. Scheme 12.9 gives some examples of enantioselective epoxidation of allylic alcohols. 

Enantioselective epoxidation of allylic alcohols using hydrogen peroxide and chiral catalysts was first reported for molybdenum 7B) and vanadium 79) complexe. In 1980, Sharpless 80) reported a titanium system. Using a tartaric acid derivative as chiral auxiliary it achieves almost total stereoselection in this reaction. 

The C = C bond in the hydroxy allylic system of a fluoroalkanol can be selectively epoxidized without affecting the hydroxy group. Enantioselective epoxidation of racemic unsaturated fluoro alcohols by using the chiral Sharpless reagent can be exploited for the kinetic resolution of enantiomers. The recovered stereoisomer (e.g., 1) has 14-98% enantiomeric excess.165... 

Allylic and homoallylic alcohols are particularly good substrates for epoxidation by TBHP/Vv and TBHP/ MoVI catalysts, with the former being superior in activity and selectivity (equations 70-72).57,226,242 Allylic alcohols have also been shown to be particularly good substrates for enantioselective epoxidation. Good results were observed in some cases with TBHP/VO(acac)2/chiral hydroxamates (equation 73),57 but a major breakthrough was obtained... 

Yamamoto has used the modularity of another type of oc-amino acid-based chiral ligand to promote enantioselective epoxidations of allylic alcohols [21]. Thus, as illustrated in Eq. (8), parallel libraries of various ligand candidates were prepared and the identity of the optimal ligand 13 was established through positional optimization. 

Stereoselective and enantioselective epoxidations have been treated in detail in recent reviews8,9. A typical example is the stereoselective epoxidation of allylic and homoallylic... 

The Sharpless Epoxidation allows the enantioselective epoxidation of prochiral allylic alcohols. The asymmetric induction is achieved by adding an enantiomerically enriched tartrate derivative. 

Chiral Mo complexes bearing ligands derived from a (2S,4R)- or (2S,4S)-4-hydroxyproline compound (13a and 13b) have been tethered to the internal surface of a mesoporous zeolite USY (251). The supported asymmetric Mo catalyst was tested for the enantioselective epoxidation of allylic alcohols. 

Achiral primary allylic alcohols undergo enantioselective epoxidation (cf. Figure 3.35), whereas—chiral primary allylic alcohols undergo diastereoselective oxidation. So the reagent... 

Fig. 3.37. Mechanistic details of Sharpless epoxidations, part II preferred transition state of enantioselective epoxidations of achiral primary allylic alcohols in the presence of l-(+)-DET (top) or d-(-)-DET (bottom).

The ratio of jy -epoxide (shown above) to anti-epoxide is 10—25 1 with TYZORTPT catalysis, whereas vanadylacetylacetonate is less selective and / -chloroperoxybenzoic acid gives the reverse 1 25 ratio. It is supposed that TYZOR TPT esterifies the free hydroxyl, then coordinates with the peroxide to favor syn-epoxidation (135). This procedure is related to that for enantioselective epoxidation of other allylic alcohols in 9—95% enantiomeric excess (135). Titanates trigger peroxide-initiated curing of unsaturated polyesters to give products of superior color, compared to conventional cobalt-initiated... 

ENANTIOSELECTIVE EPOXIDATION OF ALLYLIC ALCOHOLS (2S,3S)-3-PR0PYL0XIRANEMETHAH0L (Oxiranemethanol, 3-Propyl-, (2S,3S)-)... 

Sharpless asymmetric epoxidation ° is an enantioselective epoxidation of an allylic alcohol with ferf-butyl hydroperoxide (f-BuOOH), titanium tetraisopropoxide [Ti(0-fPr)4] and (-b)- or (—)-diethyl tartrate [(-b)- or (—)-DET] to produce optically active epoxide from achiral allylic alcohol. The reaction is diastereoselective for a-substituted allylic alcohols. Formation of chiral epoxides is an important step in the synthesis of natural products because epoxides can be easily converted into diols and ethers. 

A polyoxometalate is also at the heart of an enantioselective epoxidation of allylic alcohols using a C-2 symmetric chiral hydroperoxide 39 derived from l,l,4,4-tetraphenyl-2,3-0-isopropylidene-D-threitol (TADDOL). Thus, in the presence of the oxovanadium(IV) sandwich-type POM [ZnW(V0)2(ZnW9034)2]12- and stoichiometric amounts of hydroperoxide 39, the dienol 40 is converted to the (2R) epoxide 41 in 89% yield and 83% ee. The proposed catalytic cycle invokes a vanadium(V) template derived from the POM, substrate, and hydroperoxide, a hypothesis supported by the lack of enantioselectivity with unfunctionalized alkenes. The catalytic turnover is remarkably high at about 40,000 TON <03OL725>. 

As far as the epoxidation of enantiomerically pure acyclic allylic alcohols is concerned, the Katsuki-Sharpless enantioselective epoxidation process can be applied (see Section 4.5.2.4.1. and Houben-Weyl, Vol. E13/2, p 1219, and Table 148, pp 1226-1230). If matched substrate/ catalyst combinations are employed, many, otherwise unselective, epoxidations may be rendered highly diastereoselective. 

Figure 2. Enantioselective epoxidation of allylic alcohols hy the Sharpless method...

Enantioselective epoxidation of an allylic alcohol with the Sharpless reagent (12.15)... 

Ti(OPr )4/Bu OOH/tartrate ester (Sharpless oxidation) (titanium isopropoxide/t-butyl hydroperoxide dialkyl tartrate) Dichloromethane -20 enantioselective epoxidation of allylic alcohols... 

Through studies of Li and NMR spectra of 88 and 89 in various proportions, the formation of the mixed dimer 90 was identified as the catalyst responsible for enantioselective epoxide rearrangements to chiral allylic alcohols <2001J(P1)3054> (Scheme 18). 

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