Oxidation Sharpless

This method has proven to be an extremely useful means of synthesizing enantiomeri-cally enriched compounds. Various improvements in the methods for carrying out the Sharpless oxidation have been developed.56 The reaction can be done with catalytic amounts of titanium isopropoxide and the tartrate ligand.57 This procedure uses molecular sieves to sequester water, which has a deleterious effect on both the rate and enantioselectivity of the reaction. 

Earlier on in our work, we also used the other legendary Sharpless oxidation, the asymmetric epoxidation [22] for the transformation of the allylic alcohol 17 into the epoxide 18. In the presence of (+)-diethyl tartrate, 17 was converted... 

Alkynylepoxy alcohols of high enantiomeric purity, obtained via Sharpless oxidation of allylic alcohols (see Section D.4.5) react smoothly with excess dialkylcuprate/magnesium bromide to give (/Vf.25)-3.4-alkadiene-1.2-diols in reasonable overall yield and with high anti selectivity when performed at low temperature and by using the dimethyl sulfide complex of copper(I) bromide to synthesize the cuprates42. 

We (J. Org. Chem. 2004,69, 7234) used the power of the Sharpless oxidations to convert the prochiral 10 into the epoxy diol 11. Base-catalyzed cascade cyclization then converted 11 into crystalline 12, again with high diastereomeric and enantiomeric purity. An advantage of this approach is that by changing the absolute sense of the epoxidation and/or the dihydroxylation, it should be possible to selectively prepare each of the four enantiomerically-pure diastereomers of 12. 

Spiro-y-lactones. This anion (1) has been used to prepare steroidal 17-spiro-y-lactones (equation 1) by reaction of a 17-keto steroid at the y-position. The Sharpless oxidation step can be conducted in the presence of a A4-3-keto group. When the... 

The two enantiomeric forms of the diethyl tartrate ligand in Sharpless oxidation lead to epoxy alcohols 22 and 24. Which of the isomeric ligands is required for the present reaction ... 

The asymmetric oxidation of sulphides to chiral sulphoxides with t-butyl hydroperoxide is catalysed very effectively by a titanium complex, produced in situ from a titanium alkoxide and a chiral binaphthol, with enantioselectivities up to 96%342. The Sharpless oxidation of aryl cinnamyl selenides 217 gave a chiral 1-phenyl-2-propen-l-ol (218) via an asymmetric [2,3] sigmatropic shift (Scheme 4)343. For other titanium-catalysed epoxidations, see Section V.D.l on vanadium catalysis. 

Catalytic Asymmetric Synthesis Sharpless Oxidations of Allylic alcohols... 

Epoxy alcohols (A in Figure 17.43) are accessible in enantiomerically pure form via the Sharpless oxidation (Figure 3.35). The epoxide substructure of these compounds can be reduced to obtain an alcohol in a regiocontrolled fashion to afford an enantiomerically pure 1,3-diol, B, or an enantiomerically pure 1,2-diol, C (Figure 17.43). The 1,3-diols B and the 1,2-diols C are best accessible via reduction of A with Red-Al [NaAlH2(OCH2CH2 OCH3)2] or DIBAL, respectively. 

Cyclohexyl selenides 162 can be prepared from the 4-substituted cyclohexanones via the selenoketals and upon oxidation with chiral oxidants, compounds 163 were obtained in high yields and with excellent stereoselectivities. Some representative examples are summarized in Table 5 and it is obvious that only the Davies oxidant 158 is leading to high enantiomeric excesses in the product 163 whereas under Sharpless oxidation conditions no selectivity is obtained. The titanium complex formed in the Sharpless oxidant may promote the racemization of the intermediate selenoxide by acting as a Lewis acid catalyst, while the aprotic nature of the Davies oxidant 158 slows down racemization dramatically. 

Sharpless oxidation of the oxazole 52 provides an intermediate epoxide, which is attacked by the neighboring amino group, eventually leading to the pyrrolo[2,3-r/ isoxazole 53 (Equation 12). Variation of the aryl substituent provided access to a set of related derivatives in excellent yields <2006TL4957>. 

The key for the commercial success of the enantioselective oxidation of allylic alcohols relies mainly on the low cost of both the catalyst and the chiral auxiliary. Potential problems with the Sharpless oxidation system arise from the need to handle large amounts of hydroperoxides for large scale work and the moderate to low catalytic activity. 

Intramolecular ene reaction,3 A key step in a new route to anthracyclinones such as y-citromycinone (4) is a regioselective intramolecular ene reaction of the unsaturated aldehyde 1 to give 2 in 93% yield. Sharpless oxidation [(CH3)3COOH, VO(acac)2] of 2 is regioselective, giving the desired epoxide 3 as the only isomer. Synthesis of 4 is... 

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