Epoxides using allylic alcohols

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 (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

The Sharpless-Katsuki asymmetric epoxidation (AE) procedure for the enantiose-lective formation of epoxides from allylic alcohols is a milestone in asymmetric catalysis [9]. This classical asymmetric transformation uses TBHP as the terminal oxidant, and the reaction has been widely used in various synthetic applications. There are several excellent reviews covering the scope and utility of the AE reaction... 

Andersson also showed that, in addition to meso-desymmetrization, kinetic resolution of some cyclic epoxides by use of the first-generation catalyst was also possible, giving both epoxides and allylic alcohols in good yields (Scheme 7.51) [108], Kozmin reported the effective use of the same catalyst in the desymmetrization of diphenylsilacyclopentene oxide. The resulting products could be used in the ster-eocontrolled syntheses of various acyclic polyols (Scheme 7.52) [109]. 

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 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. 

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... 

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... 

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... 

Table 5.1 Catalytic asymmetric epoxidation of allylic alcohols using a combination of titanium wopropoxide. enantiomerically pure tartrate ester ((+)-DET or (+)-DIPT) and rerr-butyl hydroperoxide (yield and enantiomeric excess, according to the relevant publication). ...

This method, specific for the epoxidation of allylic alcohols, gives good results if the reaction is carried out under strictly anhydrous conditions, otherwise the yield or the enantiomeric excess can decrease, sometimes dramatically. This can explain the small differences between the results obtained during the validation experiments and the published results. All the different reagents are commercially available they can be used as received but in case of low yield and/or enantiomeric excess they should be distilled and dried under an inert atmosphere. Table 5.1 gives some other examples of substrates which can be epoxidized using the procedure described above. 

Poly(octamethylene tartrate) can be used directly in place of dialkyl tartrates in the Sharpless epoxidation of allylic alcohols. 

One of the earliest and most important discoveries in metal-catalyzed asymmetric synthesis is Sharpless s Ti-catalyzed epoxidation of allylic alcohols. A mere mention of all the total syntheses that have used this technology would require a separate review article Here, we select Trost s masterful total synthesis of solamin (100, Scheme 14), for its beautiful and multiple use of Sharpless s asymmetric epoxidation.1161 Optically pure epoxy alcohol 95 is converted to both epoxy iodide 96 and diol 97 The latter two intermediates are then united to give 98, which is oxidized and converted to dihydrofuran 99 by a Ramberg-Backlund transformation. The Re catalyzed butenolide annulation that is used to afford the requisite unsaturated lactone only adds to the efficiency of this beautiful total synthesis. 

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... 

It should be added that many other groups have contributed to the predevelopments of these inventions and also to later developments. All four reactions find wide application in organic synthesis. The Sharpless epoxidation of allylic alcohols finds industrial application in Arco s synthesis of glycidol, the epoxidation product of allyl alcohol, and Upjohn s synthesis of disparlure (Figure 14.4), a sex pheromone for the gypsy moth. The synthesis of disparlure starts with a Ci3 allylic alcohol in which, after asymmetric epoxidation, the alcohol is replaced by the other carbon chain. Perhaps today the Jacobsen method can be used directly on a suitable Ci9 alkene, although the steric differences between both ends of the molecules are extremely small ... 

A more recent approach to the epoxidation of allylic alcohols makes use of a vanadium polyoxometallate, together with a sterically demanding chiral tartrate (or TADDOL) -derived hydroperoxide, to give a highly chemoselective, regiose-lective and enantioselective outcome (Figure 11.2). ... 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

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. 

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

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

---