Sharpless procedure

Diketones. The Sharpless procedure for oxidation of alkenes with NaIO catalyzed by Ru02 (11,462-463) is equally efficient for oxidation of alkynes to 1,2-diones. In fact, alkenes and alkynes react at a similar rate, but ether, epoxide, and ester groups are stable to the reagent. A 1-silylacetylene is oxidized to an acylsilane. Yields are moderate to high.1... 

Cyclic allyl peroxides are converted stereoselectively into the dihydroxypropyl peroxides using a modified Sharpless procedure with osmium tetroxide and /-butyl peroxide in the presence of benzyltrimethylammonium acetate [23]. Yields are generally good with exclusive an/f-addition with respect to the peroxy group, although both the steroselectivity and yield (<40%) are poor for the oxidation of 2,3-dihydrofuran-3-yl peroxide and 2,3-dihydro-4//-pyran-4-yl peroxide. 

Asymmetric dihydroxylation can be achieved using osmium tetroxide in conjunction with a chiral nitrogen ligand. " The very successful Sharpless procedure uses the natural cinchona alkaloids dihydroquinine (DHQ) and its diastereomer dihy-droquinidine (DHQD), as exemplified in the epoxidation of imni-stilbene... 

Oxidation of 338 by the Sharpless procedure 431) gave the chiral epoxide... 

Similar surfactants based upon glucopytanose were synthesized using the Gao and Sharpless procedure for preparation of the cyclic sulfate from methyl a-D-glucopyranoside 252 using a mixture of DMF and ethyl acetate (1 1) as solvent, the axial cyclic sulfite 253 was formed exclusively, as indicated by H NMR spectroscopy, from which the cyclic sulfate 65 was obtained in good yield (Scheme 42) <1999S621>. 

This reaction was used to introduce the final two skeletal carbons in a total synthesis of maytansine (4).2 The reaction of the 2,/ -unsaturated aldehyde (2) with I (R = C6H5) gives the desired 4,5-unsaturated 3-hydroxy ester 3 in 80% yield. The ratio of the desired (S)-alcohol to the epimer is 93 7. The resulting amino acid was cyclized to the lactam in 80% yield with mesitylenesulfonyl chloride (8, 318-319). Epoxidation by the Sharpless procedure (9, 78 79) was also highly stereoselective, giving the desired epoxide and the undesired epimer in the ratio > 200 1. 

In the case of a 17-keto steroid the reaction proceeds in higher yield when Li1 is replaced with +ZnCl. The Sharpless procedure can be used for the epoxidation step. 

Application of the Sharpless procedure for the kinetic resolution of racemic allyl alcohols [Ti(0/Pr)4 BuOOH and L- or D-DET] to such a process provided an optically active dihy-drop)Tan together with enantiomerically pure unreacted furylcarhinol [6]. The Casiraghi approach leads to 2,3-unsaturated furanoses (or amino furanoses) hy an acid-catalyzed reaction of 2-(trimethylsilyloxy)furan with sugar aldehydes or aminoaldehydes. 

Sharpless s successful use of his chiral epoxidation technology has been discussed in Section 2, Scheme 2,15. Using the Sharpless procedure, Corey, Hashimoto, and Barton also described an analogous, though somewhat longer. 

The Payne rearrangement of epoxy-alcohols is a special case of an intramolecular nucleophilic opening of epoxides and is of particular synthetic utility when it is applied to epoxides from the Sharpless procedure. ... 

Keinan prepared separately the two fragments (the THF moiety and the Y-methyl-y-lactone) and used, as a key step of his sequence, the asymmetric dihydroxylation (AD-mix.-p), the very efficient Sharpless procedure for the formation of a,(3-diols. Then, the cross-coupling was performed by addition of an alkyne and a vinyl halide in the presence of palladium and copper catalysts (Fig. 6). Treatment of the unsaturated ester 48 (prepared in 4 steps from commercially available starting material, and 65 % overall yield) with AD-mix.-p in rerr-butanol/water (1 1) with methanesulfonamide for 16 h at 0 °C afforded the lactone 49 which possessed 3 carbon atoms out of the 4 with the desired absolute configuration. Inversion of the fourth stereocentre after acetonide... 

Other metal-based epoxidation catalysts have been explored to overcome some of the hmitations of the Sharpless procedure. One drawback with the Sharpless asymmetric epoxidation is the slightly lower ees often obtained when using cis-olefin substrates. The group of Yamamoto have achieved highly enantioselective epoxidations of ds-alkenes using vanadium(V) oxytriisopropoxide in the presence of C2-symmetric bishydroxamic acid ligands such as (4.23). In contrast to the Sharpless procedure this process is not hampered by the presence of air or... 

The Sharpless procedure for effecting osmium-catalyzed ligand-accelerated asymmetric dihydroxylation was utilized successfully the reaction could also be scaled up. Bis(3-methylthien-2-yl) ketone (59) was also a product in these reactions and was accompanied by an impurity whose structure has not been elucidated. Optimum yields of the dihydroxy material were obtained in dioxane-water/t-butanol-water mixtures. Use of osmium tetroxide instead of potassium osmate led to a slower reaction and increased the formation of undesired products. The material derived from synthesis revealed complete identity with the tablet degradates Any diastereomers that formed were not resolved under our chromatographic conditions. Attempted functionalization of the vicinal dihydroxy groups (acetate, acetonide, trflate) was unsuccessful and led to complex mixtures of products. 

Q In case of the enantio-selective epoxidation of allyl alcohol to glycidol, the Sharpless procedure, as conducted by ARCO, has to compete with an enzymatic resolution process from DAISO however, for the preparation of disparlure the Sharpless epoxidation proves unsurpassed. 

Chiral epoxy alcohols, which are not easily available via the Sharpless procedure [391], were successfully resolved with PPL (Scheme 2.55). Interestingly, the lipase is not deactivated by a possible reaction with the epoxide moiety and it is able to accept a large variety of structures [392, 393]. The significant influence of the... 

As can be seen from the above example, there are two important differences from the normal Sharpless procedure first, because the sulphoxide is a good ligand for titanium, the reaction must be performed with a stoichiometric quantity of tartrate/titanium tetraisopropoxide second, one equivalent of water is necessary for good e.e.s. If water is strictly excluded, the enantiomeric excess drops... 

Several new developments in enantioselective C-O ring construction have been applied in the s mtheses of natural products. To achieve control, the oxygenated quaternary center of dysiherbaine 9 must be established under kinetic conditions. One approach would be Sj 2 opening, but this would require displacement at a fully-substituted center. Susumi Hatakeyama of Nagasaki University has shown (Chem. Commun. 2007, 4158) that the epoxide 6, prepared by the Sharpless procedure, undergoes just such an opening under mild acid catalysis. 

The excellent enantioselectivities generally achieved with titanium tartrate-catalyzed epoxidation of allylic alcohols with ferf-butylhydroperoxide was exploited, for example, for the preparation of (2S,3S)- and (2/ ,3f )-[2,3- H2]oxiranes (72), two valuable chiral building blocks (Figure 11.28). By using a slightly modified Sharpless procedure, ( )-3-triphenylsilyl-2-[2,3- H2]propenol (20) was converted into the (S,S)- and (/ ,/ )-forms, respectively, of 3-triphenylsilyl[2,3- H2]glycidol (71). The hydroxylmethyl substituent... 

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