Oxidation Sharpless epoxidation

Introduction Catalytic methods of asymmetric induction Part I - Sharpless Asymmetric Epoxidation The AE Method The ligands The catalyst Catalyst structure The mnemonic device The synthesis of propranolol Modification after Sharpless Epoxidation Oxidation after Sharpless epoxidation The Payne rearrangement... 

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. 

Finally, the necessity arose for the synthesis of pentulose 21, labeled with, 3C on the central carbons, C-2 and C-3, for an independent biosynthetic study, which is reported in Section III.5.27 The doubly labeled ester 34 (Scheme 14) is readily available by a Wittig- Homer condensation of benzyloxyacetaldehyde with commercially available triethylphosphono-(l,2-l3C2)acetate. Chirality was introduced by the reduction of ester 34 to the allylic alcohol, which produced the chiral epoxide 35 by the Sharpless epoxidation procedure. This was converted into the tetrose 36, and thence, into the protected pentulose 37 by the usual sequence of Grignard reaction and oxidation. 

Fig. 12.4. Successive models of the transition state for Sharpless epoxidation. (a) the hexacoordinate Ti core with uncoordinated alkene (b) Ti with methylhydroperoxide, allyl alcohol, and ethanediol as ligands (c) monomeric catalytic center incorporating t-butylhydroperoxide as oxidant (d) monomeric catalytic center with formyl groups added (e) dimeric transition state with chiral tartrate model (E = CH = O). Reproduced from J. Am. Chem. Soc., 117, 11327 (1995), by permission of the American Chemical Society. 

Epoxide-derived radicals are generated under very mild reaction conditions and are therefore valuable for intermolecular C-C bond-forming reactions [27,29]. The resulting products, 5-hydroxyketones, 5-hydroxyesters or 5-lactones constitute important synthetic intermediates. The first examples were reported by Nugent and RajanBabu who used a variety of epoxides, such as cyclohexene oxide and a Sharpless epoxide (Scheme 7). 

Omura devised an efficient asymmetric synthesis of the 3a-hydroxyfuroindoline ring system required for the total synthesis of madindoline A (172) and B <00JA2122>. Thus, Sharpless asymmetric oxidation of tryptophol (170) led to the desired product 171 in 99% ee in a fashion consistent with the Sharpless epoxidation mnemonic <80JA5976>. 

It is now clear that asymmetric catalytic hydrogenation is rather successful. However, the initial research work of Sharpless [5] in the asymmetric epoxidation, followed by the results of Jacobsen et al. [6] opened large opportunities for liquid-phase asymmetric oxidation. Sharpless epoxidation has been widely applied in bench-scale organic synthesis, and more recently, salene derivatives emerged among the most effective catalysts in this reaction [7,8],... 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

In this chapter, the ligand design for the catalytic enantioselective oxidations developed after the Katsuki-Sharpless epoxidation and the Sharpless AD will be discussed. 

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). 

Semen, reactive oxygen species, 612 Sensorial quaUty appreciation, oxidation stabihty, 664 Semm protein oxidative damage, 614 see also Human seram Sesquiterpenes, stractural chemistry, 133-6 SET see Single electron transfer Sharpless epoxidation, allylic alcohols, 789 Shelf durability, peroxide value, 656 Ship-in-the-bottle strategy, chiral dioxetane synthesis, 1176-7... 

The formation of methylperoxy intermediates—i.e., the product of a formal insertion of O2 into the metal-methyl bond—was substantiated by the observation of epoxidation of allylic alkoxides (Scheme 6), in analogy to the proposed mechanism for the Sharpless epoxidation utilizing tert-butylhydroperoxide (TBHP). A similar oxygen atom transfer from a coordinated alkylperoxide to olefin was also postulated for the epoxidation of olefins with TBHP catalyzed by Cp Mo(0)2Cl [31]. The use of organomolybdenum oxides in olefin epoxidafion cafalysis (albeit not with O2) has recently been reviewed [32]. 

Selective polymerization, enantiomers, 185 Semico rrin-copper complexes, 199 Sharpless epoxidation, racemic alcohols, 45 Side-chain units, prostaglandins, 310 Sigmatropic reactions, 222 Silanes, oxidative addition, 126 Silica gel, 285, 352... 

The (panial) description of the synthesis and coupling of the live fragments starts with the cyclohexyl moiety C21—CM The first step involved the enantio- and diastereoselective Sharpless epoxidation of l,4-pentadien-3-ol described on p 126f The epoxide was converted m four steps to a 3-vinyl 6-lactone which gave a 3-cydohexenecarboxylate via Ireland-Claisen rearrangement (cf p 87) Uncatalysed hydroboration and oxidation (cf. p 131) yielded the desired muis-2-methoxycydohexanol which was protected as a silyl ether The methyl car-... 

Catalytic reactions in Sharpless epoxidation were achieved in 1986 by addition of molecular sieves, which suppress the formation of nonenantioselective complexes by moisture already present in the medium or produced during the reaction [33]. Similar problems needed to be solved in the asymmetric oxidation of sulfides because a decrease in the concentration of a... 

The known allylic alcohol 9 derived from protected dimethyl tartrate is exposed to Sharpless asymmetric epoxidation conditions with (-)-diethyl D-tartrate. The reaction yields exclusively the anti epoxide 10 in 77 % yield. In contrast to the above mentioned epoxidation of the ribose derived allylic alcohol, in this case epoxidation of 9 with MCPBA at 0 °C resulted in a 65 35 mixture of syn/anti diastereomers. The Sharpless epoxidation of primary and secondary allylic alcohols discovered in 1980 is a powerful reagent-controlled reaction.12 The use of titanium(IV) tetraisopropoxide as catalyst, tert-butylhydro-peroxide as oxidant, and an enantiopure dialkyl tartrate as chiral auxiliary accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity. If the reaction is kept absolutely dry, catalytic amounts of the dialkyl tartrate(titanium)(IV) complex are sufficient. 

A reaction of furylbutenol 37 under Sharpless asymmetric oxidation conditions afforded the epoxide 38, which was further converted into an antitumor antibiotic, asperlin 39 <95H425>. 

An evolution from Noyori s approach leads to one where a diethylaminomethyl substituent is used to give a one-carbon start to the a-chain. From this synthon there is much flexibility because the co- and a-chains can be added in either order, and synthesis of the single isomer synthon can start with a Sharpless epoxidation. This route is shown in Scheme 30.6.23 For completeness, we note that there is another variant of the general enone approach identified by Danishefsky, in which the C-9 and C-ll carbon oxidation states are inverted (ketone at what is to become C-ll) where the a-chain is added first as a nucleophile, and then the co-chain is added second as an electrophile.24... 

The first samples were obtained by resolution.191193 Because the last step in the synthesis of the racemate is the oxidation of the sulfide to the sulfoxide,194-198 this has been modified to provide the S-isomer (Scheme 31.15). This is achieved by the Kagan method, which is a variation of the Sharpless epoxidation (see Chapter 9).199 200... 

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