Epoxidation, of allyl alcohols

Propylene oxide-based glycerol can be produced by rearrangement of propylene oxide [75-56-9] (qv) to allyl alcohol over triUthium phosphate catalyst at 200—250°C (yield 80—85%) (4), followed by any of the appropriate steps shown in Figure 1. The specific route commercially employed is peracetic acid epoxidation of allyl alcohol to glycidol followed by hydrolysis to glycerol (5). The newest international synthesis plants employ this basic scheme. 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

Asymmetric catalytic epoxidation of allylic alcohols 93MI2. 

Scheme 3. Asymmetric epoxidation of allylic alcohol 12 double asymmetric induction.

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... 

Asymmetric epoxidations of alkenes have been intensively studied since Sharpless initial report on asymmetric epoxidation of allylic alcohols in 1980. This reaction, discussed in Section 9.1.3, has become one of the most widely employed reactions in asymmetric synthesis, due to its reliability and high enantioselectivity [2],... 

Ten years after Sharpless s discovery of the asymmetric epoxidation of allylic alcohols, Jacobsen and Katsuki independently reported asymmetric epoxidations of unfunctionalized olefins by use of chiral Mn-salen catalysts such as 9 (Scheme 9.3) [14, 15]. The reaction works best on (Z)-disubstituted alkenes, although several tri-and tetrasubstituted olefins have been successfully epoxidized [16]. The reaction often requires ligand optimization for each substrate for high enantioselectivity to be achieved. 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

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. ... 

Sharpless and co-workers have shown how, with a catalyst developed by Sharpless, the rate and selectivity in a,symmetric epoxidation of allylic alcohols can be improved substantially by using molecular sieve 3 A / 4 A (Gao et al., 1987). In some ca.ses, the use of molecular sieves has allowed asymmetric epoxidation, which was not possible with the original catalyst. 

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 epoxidation of allylic alcohols can also be effected by /-butyl hydroperoxide and titanium tetraisopropoxide. When enantiomerically pure tartrate ligands are included, the reaction is highly enantioselective. This reaction is called the Sharpless asymmetric epoxidation.55 Either the (+) or (—) tartrate ester can be used, so either enantiomer of the desired product can be obtained. 

Epoxides of allylic alcohols exhibit chelation-controlled regioselectivity.128... 

To account for stereochemical results for the epoxidation of allyl alcohols, a slightly different intermediate has been proposed as shown in Fig. 6.9.16 The authors propose an intermediate (A) analogous to the intermediate in peracid oxidations. A small molecule of alcohol or water is coordinated to Ti with deprotonation and another is coordinatively ligated to Ti without deprotonation to achieve a pentacoordinated ligand sphere. During epoxidation, the allyl alcohol substrate is held in position by a hydrogen bond. 

FIGURE 6.9 Proposed mechanism for epoxidation of allyl alcohols.16... 

The catalyst was used for the epoxidation of allylic alcohols at room temperature using t-butyl hydroperoxide as the oxidant. The activity of the heterog-enized catalyst is comparable with that of the free complex, yielding products with excellent yields and selectivity and moderate enantioselectivity.185... 

Metal alkoxides undergo alkoxide exchange with alcoholic compounds such as alcohols, hydro-xamic acids, and alkyl hydroperoxides. Alkyl hydroperoxides themselves do not epoxidize olefins. However, hydroperoxides coordinated to a metal ion are activated by coordination of the distal oxygen (O2) and undergo epoxidation (Scheme 1). When the olefin is an allylic alcohol, both hydroperoxide and olefin are coordinated to the metal ion and the epoxidation occurs swiftly in an intramolecular manner.22 Thus, the epoxidation of an allylic alcohol proceeds selectively in the presence of an isolated olefin.23,24 In this metal-mediated epoxidation of allylic alcohols, some alkoxide(s) (—OR) do not participate in the epoxidation. Therefore, if such bystander alkoxide(s) are replaced with optically active ones, the epoxidation is expected to be enantioselective. Indeed, Yamada et al.25 and Sharp less et al.26 independently reported the epoxidation of allylic alcohols using Mo02(acac)2 modified with V-methyl-ephedrine and VO (acac)2 modified with an optically active hydroxamic acid as the catalyst, respectively, albeit with modest enantioselectivity. 

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... 

A combination of DAT and a metal alkoxide other than titanium alkoxide serves as a poor catalyst for the epoxidation of allylic alcohols. However, the combination of DAT and silica-supported tantalum alkoxides (2a) and (2b) prepared from Ta(=CHCMe3)(CH2Cme3)3 and silica(5oo) shows high enantioselectivity in the epoxidation of E-allylic alcohols, though chemical yields are not very great (Scheme 4).3... 

Al(OtBu)3 can be used for epoxidation of allylic alcohols in the presence of a stoichiometric amount of BuOOH with high selectivity (Scheme 70).307... 

Another interesting asymmetric epoxidation technique using metal catalysis involves the vanadium complexes of A-hydroxy-[2.2]paracyclophane-4-carboxylic amides (e.g., 19), which serve as catalysts for the epoxidation of allylic alcohols with f-butyl hydroperoxide as... 

The models proposed for the Ru(III) and Ru(EDTA) catalyzed epoxidation of allyl alcohol replace each other in the corresponding reactions of cyclohexene. Thus, mono-nuclear and di-nuclear paths were reported for the Ru(III) and Ru(EDTA) catalysis, respectively (145,146). 

ASYMMETRIC EPOXIDATION OF ALLYLIC ALCOHOLS SHARPLESS EPOXIDATION... 

The development of transition metal mediated asymmetric epoxidation started from the dioxomolybdcnum-/V-cthylcphcdrinc complex,4 progressed to a peroxomolybdenum complex,5 then vanadium complexes substituted with various hydroxamic acid ligands,6 and the most successful procedure may now prove to be the tetroisopropoxyltitanium-tartrate-mediated asymmetric epoxidation of allylic alcohols. 

TABLE 4-1. Asymmetric Epoxidation of Allylic Alcohols by Sharpless Reagents (Method A) and by the Modified Sharpless Reagents (Method B)... 

Canali et al.17 reported the use a linear poly(tartrate) ligand in the asymmetric epoxidation of allylic alcohols. Moderate results were obtained. They also reported the use of branched/crosslinked poly(tartrate), which gave moderate to good results in the asymmetric epoxidation of allylic alcohols. As shown in Scheme 4-9, when L-(+)-tartaric acid and 1,8-octanediol are heated... 

As a further example of a hydroxyl-assisted epoxidation, geraniol and nerol bearing two isolated C=C double bonds were regioselectively epoxidized with TS-1 at the 2-position (near the OH group), as reported by Kumar et al. (795). On the basis of these results, Kumar et al. (195) proposed that the transition state of the epoxidation of allylic alcohols involves coordination of the alcoholic functional group to the Ti active site and that the double bond interacts with one of the peroxidic oxygen atoms, not with the titanium site (Scheme 9). 

Epoxidation of allyl alcohols can generate two isomers, the threo- and erythro-epoxides (Schemes 11 and 12). Control of the relative amounts of the two isomers... 

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