Sharpless epoxidation of allylic alcohols

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... 

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

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 ... 

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). 

Isomerization of primary allylic alcohols proceeds in dichloromethane at 25 °C in the presence of a catalyst prepared in situ from VO(acac)2 or Mo02(acac)2 and BTSP to give tertiary isomers in good yields. This is in sharp contrast to the well-known Sharpless epoxidation of allylic alcohols. The catalysts are also effective for rearrangements of secondary-tertiary allylic alcohols. The isomerization of an allenyl allylic... 

Contrary to the optical resolutions described in Sections 2.1.1.-2.1.3., which depend on the solubility or chromatographic properties ( Thermodynamic resolution ), the kinetic resolution rests on rate differences shown by the enantiomers when reacted with an optically active reagent. In the ideal case, only one enantiomer is converted into the envisaged product and the other enantiomer is unchanged. In this way, optical resolution is reduced to the more simple separation of two different reaction products. In practice, only two methods of kinetic resolution are reasonably general and reliable the Sharpless epoxidation of allylic alcohols and the enzymatic transesterification of racemic alcohols or carboxylic acids. 

The Sharpless epoxidation of allylic alcohols with lert-butyl hydroperoxide/titanium tetraiso-propoxide/diisopropyl tartrate (DIPT) is a highly enantioface-selective reaction and follows the topicity shown51. 

FIGURE 9.1 Face selectivity for the Sharpless epoxidation of allyl alcohols. 

A considerable amount of work was required to optimize the leaving group and avoid racem-ization through a Payne rearrangement mechanism.12 Of course, the Sharpless epoxidation of allyl alcohols is well-known to access these 3-functionalized epoxides. 

Fig. 3.7. Definition of the enantiomeric excess ee using the Sharpless epoxidation of allylic alcohol as an example. The chiral auxiliary is tartaric acid diethyl ester (diethyl tartrate, DET).

The quality of enantioselective reactions is numerically expressed as the so-called enantiomeric excess (ee). It is equal to the yield of the major enantiomer minus the yield of the minor enantiomer in the product whose total yield is normalized to 100%. For example, in the Sharpless epoxidation of allyl alcohol (see Figure 3.7). S - and R-glycidol are formed in a ratio of 19 1. For a total glycidol yield standardized to 100%, the S-glycidol fraction (95% yield) thus exceeds the /f-glycidol fraction (5% yield) by 90%. Consequently, S-glycidol is produced with an ee of 90%. 

Chiral epoxides are important intermediates in organic synthesis. A benchmark classic in the area of asymmetric catalytic oxidation is the Sharpless epoxidation of allylic alcohols in which a complex of titanium and tartrate salt is the active catalyst [273]. Its success is due to its ease of execution and the ready availability of reagents. A wide variety of primary allylic alcohols are epoxidized in >90% optical yield and 70-90% chemical yield using tert-butyl hydroperoxide as the oxygen donor and titanium-isopropoxide-diethyltartrate (DET) as the catalyst (Fig. 4.97). In order for this reaction to be catalytic, the exclusion of water is absolutely essential. This is achieved by adding 3 A or 4 A molecular sieves. The catalytic cycle is identical to that for titanium epoxidations discussed above (see Fig. 4.20) and the actual catalytic species is believed to be a 2 2 titanium(IV) tartrate dimer (see Fig. 4.98). The key step is the preferential transfer of oxygen from a coordinated alkylperoxo moiety to one enantioface of a coordinated allylic alcohol. For further information the reader is referred to the many reviews that have been written on this reaction [274, 275]. 

Optically active a ,/3-epoxyaldehydes are readily available via Sharpless epoxidation of allyl alcohols followed by oxidation. Studies by Heydari on the addition of fran -substituted a,/3-epoxyaldehydes to tri-n-butylallylstannane provide a general method for the synthesis of the corresponding yn-alcohols (9) with high selectivity (Scheme 6.3.5). 

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 Sharpless epoxidation of allylic alcohols gives rise to moderate asymmetric amplification [5, 13]. One example is shown in Scheme 2. The epoxidation of chalcone by a hydroperoxide in the presence of a catalyst formed by the combination of (E)-BINOL and YfOi-Prfj, displays a similar asymmetric amplification... 

The same group has applied this imino Diels-Alder reaction in an enantiosel-ective total synthesis of the alkaloid (-)-cannabisativine (Scheme 33) [70b]. An initial Sharpless epoxidation of allylic alcohol 183 provided enantiomerically pure compound 184, which could be converted in four steps to alcohol 185. This compound could then be relayed into the requisite diene 186. Imino Diels-Alder reaction of 186 led to a single cycloadduct 188, presumably via a transition state like 187. It was then possible to homologate the ester functionality of 188 via the corresponding aldehyde to acetal 189. This intermediate could be converted in several steps into 190. Another key step in the strategy was epimeriza-tion via a retro Michael reaction leading to aldehyde 191, which could be transformed in five steps into (-)-cannabisativine. 

Olefins are very important industrial raw materials, and much effort has been devoted toward using them as substrates in asymmetric synthesis [811, 812, 853], The industrial synthesis of nonracemic a-aminoacids by catalytic hydrogenation was ore of the first important uses of olefins in asymmetric synthesis [859], Today, the Sharpless epoxidation of allylic alcohols [807, 808, 809] is one of the most popular methods in asymmetric synthesis. The importance of pyrethrinoid pesticides, bearing a cyclopropane skeleton, justifies the efforts devoted to the asymmetric synthesis of cyclopropanes from alkenes [811,812, 937],... 

The Sharpless epoxidation of allyl alcohols 3.16 by /erf-butyl hydroperoxide under catalysis with chiral titanium complexes is a very popular method that has frequently been used in industry [811, 812, 853], This epoxidation was initially developed with stoichiometric amounts of tartrate catalysts. Today, it is usually performed in the presence of catalytic amounts of Ti(0/ -Pr)4 and diethyl or diisopropyl tartrate (2R,3R)- or (25,35)-2.69 (R = Et or r-Pr). The reactions are conducted at or near room temperature in the presence of molecular sieves. Several... 

The Sharpless epoxidation of allylic alcohols with tert-butylhydroperoxide and titanium(IV) isoproxide has been carried out with a polymeric tartrate made from tartaric acid and 1,8-octanediol.114 The yield of epoxide (92%) was comparable with that when dimethyl tartrate was used (91%), but the 79% ee was lower than the 98% ee found with the dimethyl tartrate. It may be possible to raise the ee by further variations in the structure of the polymer. The heterogenization of a catalyst for a homogeneous reaction often requires optimization to obtain comparable or higher yields and stereospecificity. 

P-Siloxyaldehydes. Chiral epoxy alcohols are readily available (e.g., by Sharpless epoxidation of allylic alcohols). Their transformation via a stereoselective rearrangement-silylation induced by the silyl triflate and i-Pr2NEt opens a new way to protected aldols. 

Sharpless epoxidation of allyl alcohols (Sharpless, 1985, 1988 Pfenninger, 1986 Rossiter, 1985 Woodard et al., 1991 Finn and Sharpless, 1991 Corey, I990a,b), an example of which is included in Table 9.6, is perhaps the most recent and one of the most remarkable applications of asymmetric catalysis. The reaction is normally performed at low temperatures (-30 to 0°C) in methylene chloride with a titanium complex consisting of a chiral component [diethyl tartrate (DET) or diisopropyl tartrate (DIPT)] and a titanium salt (titanium tetraisopropoxide) as the catalyst. The beauty of the synthesis is that both enantiomers of the tartrate are available so that either form of the product can be prepared in more than 90% ee. 

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