Epoxidations diastereoselectivity

Figure 9.4 shows stereogenic epoxide formations with S ylides and a ketone. The substrate is a conformationally fixed—because it represents a trans-decalin—cyclohexanone. Both the dimethylsulfoxonium methylide and the dimethylsulfonium methylide convert this cyclohexanone into an epoxide diastereoselectively. As Figure 9.4 shows, the observed diastereoselectivities are complementary. The sulfoxonium methylide attacks the carbonyl carbon equatorially, whereas the attack by the sulfonium ylide takes place axially. 

In ( )-cyclooctene systems the rate of ring inversion is lower than of epoxidation diastereoselectivities therefore strongly depend on the reaction conditions49. 

Enhancement of peracid epoxidation diastereoselectivity of allylic alcohols by double hydrogen bridging, involving functional groups with basic oxygen in homo- or bishomoallylic position, is discussed in Section 4.5.1.2.2. 

Denmark et al. reported a general protocol for the catalytic epoxidation of alkenes by in r// -generated reactive dioxiranes capable of epoxidizing a variety of alkenes under biphasic conditions <1995JOC1391>. The epoxide diastereoselectivity (Scheme 4) showed pronounced dependence on the solvent used since the ratio of diastereo-mers, as well as the distribution between epoxide and enone products, is dependent on the solvent <1995TL2437, 1999TL8023>. Selected examples are given in Table 2. 

Another possibility for enhaneing the selectivity toward epoxides is use of the urea-H202 (UHP) adduct. This enables the oxidation to be carried out in water-free solutions, thus avoiding formation of any diols and other side reactions. In the case of the oxidation of chiral allylic alcohols (see below) high diastereo-selectivities have been achieved [3]. The ability to transform olefins to epoxides diastereoselectively seems to indicate that the reaction proceeds through a peracid-like transition state. However, a drawback of the urea-H202 system is the insolubility of the polymeric complex. 

Rh2(OAc)4 catalyses Mukaiyama epoxidation of alkenes in acetone in the presence of 2 and i-PrCHO in good yields. Mono-epoxidation products for neryl and geranyl acetate are obtained in 65% and 74% yield, respectively, on decreasing the amount of aldehyde. Conditions for regioselective epoxidation and mono-epoxidation of terpenes have been established. The epoxidation diastereoselectivity increases with increasing steric bulk around the CHO group of the aldehyde. The oxidation is initiated by the O2 entrapped in Rh(II) complex. " ... 

The retrosynthetic analysis proposed by Yamamoto et is based on the asymmetric epoxidation of a homoallylic alcohol 58 obtained from (5)-limonene (Scheme 34.16). The (5)-homoallyl alcohol 58 was epoxidized diastereoselectively using hydroxamic acid 59 as ligand to give the corresponding epoxy alcohol 60 with 84% yield and 90% de. 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

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) ... 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

One of the most significant developmental advances in the Jacobsen-Katsuki epoxidation reaction was the discovery that certain additives can have a profound and often beneficial effect on the reaction. Katsuki first discovered that iV-oxides were particularly beneficial additives. Since then it has become clear that the addition of iV-oxides such as 4-phenylpyridine-iV-oxide (4-PPNO) often increases catalyst turnovers, improves enantioselectivity, diastereoselectivity, and epoxides yields. Other additives that have been found to be especially beneficial under certain conditions are imidazole and cinchona alkaloid derived salts vide infra). 

Metzner et al. also prepared the selenium analogue 17 of their C2 symmetric chiral sulfide and tested it in epoxidation reactions (Scheme 1.6) [8]. Although good enantioselectivities were observed, and a catalytic reaction was possible without the use of iodide salts, the low diastereoselectivities obtained prevent it from being synthetically useful. 

A new iterative strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays has been described by Shibasaki. This strategy relies on a highly catalyst-controlled epoxidation of a, 3-unsaturated morpholi-nyl amides promoted by the Sm-BIN0L-Ph3As=0 complex, followed by the con-... 

Epoxidation of conjugated dienes can be regioselective when one double bond is more electron-rich than the other otherwise mixtures of mono- and diepoxides will be obtained. When the alkene contains an adjacent stereocenter, the epoxidation can be diastereoselective [2]. Hydroxy groups can function as directing groups, causing the epoxidation to take place syn to the alcohol [2, 3]. 

The major limitation of asymmetric sulfur ylide epoxidations is that only aromatic vinylepoxides can be formed efficiently and with high selectivity. When an aliphatic aldehyde is allowed to react with a semistabilized or nonstabilized sulfur ylide, poor diastereoselectivities and yields are observed, due to problems in controlling the ylide conformation and competing ylide rearrangement reactions [71]. However, some racemic, aliphatic vinylepoxides have been successfully formed by sulfur ylide epoxidations, although varying diastereoselectivities were observed [78-80],... 

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]. 

The MT0/H202/pyridine system enjoys a broad substrate scope and has become the method of choice for the epoxidation of di-, tri-, and tetrasubstituted olefins. As an added benefit, it gives high diastereoselectivities for a number of cyclic dienes (Table 12.1). 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

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