Allylic alcohols directed asymmetric epoxidations

Asymmetric epoxidation of allylic alcohols is a very reliable chemical reaction. More than a decade of experience has confirmed that the Ti-tartrate catalyst is extremely tolerantof structural diversity in the allylic alcohol substrate for epoxidation yet is highly selective in its ability to discriminate between the enantiofaces of the prochiral olefin. Today the practitioner of organic chemistry need provide only the allylic alcohol to perform the reaction. All other reagents and materials required for the reaction are available from supply houses and usually are sufficiently pure as received to be used directly in the asymmetric epoxidation process. [When purchasing f-butyl hydroperoxide in prepared solutions, however, the more concentrated 5.5-M solution in isooctane (2,2,4-trimethylpentane) should always be chosen over the 3.0-M solution.] If the considerations presented in this chapter are observed, with attention to the moderately stringent technique outlined, no difficulty should be encountered in performing this reaction. 

FIGURE 35.3. Discrimination induction by hydroxyl-directed asymmetric epoxidation of allylic alcohols. 

Despite the tremendous success of hydroxyl-directed asymmetric epoxidation of allylic alcohols and homoallylic alcohols, the development of efficient asymmetric epoxidation methods for unfunctionalized olefins is still of great importance. In the mid-1980s, Kochi and co-workers studied achiral epoxidation of unfunctionalized olefins using achiral Cr(III)-salen and Mn(lll)-salen comlexes as catalysts, and they proposed that a high valent metal oxo (such as 0=Cr(V)-salen and 0=Mn(V)-salen species) as the reactive intermediate was responsible for the epoxidation of olefins. Such a reactive intermediate was formed in a catalytic cycle by oxidation of the catalyst (such as Cr(III)-salen or Mn(lll)-salen complex) with the stoichiometric oxidant (such as PhlO or NaOCl). ... 

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. 

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 ... 

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. 

Lygo, B. and To, D.C.M., Asymmetric Epoxidation via Phase-transfer Catalysis Direct Conversion of Allylic Alcohols into a, -Epoxyketones. Chem. Commun. 2002, 2360-2361. 

Enantiopure allylic alcohols are employed widely as building blocks for asymmetric synthesis, and particularly as substrates for various diasteroselective allcene functionalization reactions such as cyclopropanation and epoxidation directed by the hydroxyl group [129]. 

The mechanism of the asymmetric epoxidation of allylic alcohols with the Sharpless-Katsuki catalyst is assumed to be very similar to the one described for the Halcon-ARCO process in Section 2.5. The key point is that the chiral tartrate creates an asymmetric environment about the titanium center (Figure 18). When the allylic alcohol and the t-butyl hydroperoxide bind through displacement of alkoxy groups from the metal, they are disposed in such a way as to direct oxygen transfer to a specific face of the C=C double bond. This point is crucial to maximize enantioselectivity. 

Of particular value in complex syntheses is a technique for epoxidation that can be applied to allylic alcohols and that directs the approach of the oxidizing group to one or the other of the two faces of the double bond. This results in the formation of one enantiomeric form in excess of the other and, thus, stands as an asymmetric synthesis. The technique is simple and consists of the formation of a chiral catalyst, a coordination complex, from titanium tetra-isopropoxide and one of the optically active forms of a dialkyl tartrate. The allylic alcohol associates with this complex in a specific way and then is epoxidized on one face by t-butyl hydroperoxide. The epoxide is produced in high enantiomeric excess, frequently more than 95%. This process has been used widely in organic synthesis since its discovery in 1980. It is now known as the Sharpless epoxidation. 

Direct air epoxidation of propylene to propylene oxide suffers from selectivity problems. Epoxidation by alkyl hydroperoxide, as practiced by Arco, is based on the use of Mo(CO)g as a homogeneous catalyst. The most impressive use of homogeneous catalysis in epoxidation, however, is in the Sharpless asymmetric oxidation of allylic alcohols. In view of its importance, this enantioselective reaction is included in Chapter 9 which is devoted mainly to asymmetric catalysis. 

The Sharpless asymmetric epoxidation of allylic alcohols (one of the reactions that helped K. Barry Sharpless earn his part of the 2001 Nobel Prize) offers a good example of an enantioselective technique that can be used to create either enantiomer of an epoxide product. This reaction uses a diester of tartaric acid, such as diethyl tartrate (DET) or diisopropyl tartrate (DIPT), as the source of chirality. The dialkyl tartrate coordinates with the titanium tetraisopropoxide [Ti(Oi-Pr)4] catalyst and t-butyl hydroperoxide (r-BuOOH) to make a chiral oxidizing agent. Since both enantiomers of tartaric acid are commercially available, and each enantiomer will direct the reaction to a different prochiral face of the alkene, both enantiomers of an epoxide can be synthesized. 

The asymmetric epoxidation of all four isomeric allylic-homoallylic alcohols of the type 26 and the subsequent hydride reduction of each epoxide to both possible dideoxyheptitols has been reported. " Only three isomers of 26 undergo a diastereoselective epoxidation and it was concluded that the direction of epoxidation for E-alkenes was controlled by the chirality of the allylic alcohol, whereas for Z-configurated olefins the relative stereochemistry between the two alcohols is important. 

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