Sharpless kinetic resolution

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde. 

The combination of the preceding method of obtaining allyl alcohols with the Sharpless kinetic resolution (SKR) of secondary allyl alcohols allows conversion of the original racemic allyl alcohol into a pure enantiomer with a 100% theoretical yield. By this procedure, the glycidol obtained by the SKR epoxidation of the secondary allyl alcohol is converted into the corresponding mesylate and then treated with the Te ion, furnishing the allylic alcohol with the same configuration of the enantiomer in the SKR which... 

Sharpless kinetic resolution of y-trimethylsilyl allylic alcohols can be highly efficient in the case shown (equation 28), the epoxyalcohol and the remaining allylic alcohol were both formed in greater than 99% ee. Further synthetic applications of the product chiral... 

Fig. 3.31. Sharpless kinetic resolution of chiral racemic secondary allyl alcohols.

Sharpless catalytic asymmetric dihydroxylation of 2-vinylfuran followed by treatment of the diol product with NBS, and subsequent Jones oxidation and Luche reduction provided a highly functionalized a,(1-unsaturated y-lactone in 70% yield overall giving a key intermediate in the synthesis of phomopsolide C <02TL8195>. Similar procedures were adopted by the same authors to synthesize 2-deoxy and 2,3-dideoxyhexoses <02OL1771>. As depicted below, Sharpless kinetic resolution was also used to prepare a pyranone from a furfuryl alcohol in 38% yield, which served as the intermediate in the synthesis of (+)-isoaltholactone <02T6799>. 

The combination of the chemistry shown in Scheme 22,100 with the Sharpless kinetic resolution (SKR) of secondary allylic alcohols 46101 provides a method for the conversion of racemic allylic alcohols 46 into a single enantiomer with 100% theoretical yield.102 The reaction of sodium telluride with the mesylate 48 derived from 47 affords 46a. In this way, a single enantiomer of the allylic alcohol 46 is obtained in high yield (Scheme 23).102... 

Racemic hydroxy ester 225 was converted, via a Sharpless kinetic resolution, to the enantiomerically pure epoxide 226. This epoxide was then converted to the diol "/-lactone by intramolecular attack of the ester, assisted by nucleophilic dealkylation with iodide ion. Deprotonation and methylation anti to the alkoxide followed by acetonide formation afforded 227 in 56% yield. Dibal reduction, protection of the resulting aldehyde as the terminal olefin, silylation of the tertiary alcohol, and liberation of the aldehyde via ozonolysis provided a 45% yield of the C-9 to C-15 fragment 228. 

The remaining segment, C-3 to C-8, was constructed by a similar route. Optically active allylic alcohol 229, produced from lithio ethylacetate and methacrolein followed by a second Sharpless kinetic resolution, was hydrolized to the corresponding hydroxy acid. Neutralization followed by iodolactonization then gave 230 in 85% yield. This highly stereoselective cyclization produced a cis-trans ratio of 20 1 via a one-pot procedure. Deprotonation and methylation afforded the expected anti a-methyl compound, contaminated with about 10% of the syn compound but none of the methyl ether. Formation of the silyl ether then produced 231 in 66% yield. Dibal reduction to the aldehyde concomitant... 

Lu and Zhou [44] have utilized a reaction between an N-sulfonyl iminium ion and allyl trimethylsilane in enantioselective total syntheses of two piperidine alkaloids (Scheme 23). The initial step in this approach involved a modified Sharpless kinetic resolution of furfuryl sulfonamide 120, leading to P-amide 121... 

Figure 8.2. Origins of selectivity in the Sharpless kinetic resolution procedure.

Scheme 8.8. Reactions of a chiral allylic alcohol under Sharpless epoxidation conditions (Ti(0-i-Pr)4, /-BuOOH) using the chiral tartrates given (DIPT = diisopropyltartrate). (a) The matched case, in which the preferred approach of the asymmetric catalyst and the diastereoselectivity of the substrate are the same, (b) The mismatched case, (cj An example of a Sharpless kinetic resolution (KR).

Using a racemic allylic alcohol, one can take advantage of this rate differential to selectively epoxidize the more reactive 5 isomer in the presence of its antipode. This procedure is known as a Sharpless kinetic resolution (KR) [13,36]. The KR has very wide applicability for the preparation of both 1,2-anti epoxy alcohols and the unreacted allylic alcohol, often with very high enantioselectivities (note that the diastereomeric 1,2-syn series is not generally available by this technique). In general terms, carrying out the reaction to lower conversions will maximize the yield and... 

Figure 4.3 Sharpless kinetic resolution of racemic substrates. Abbreviation DET diethyl tartrate...

Kinetic resolution is the achievement of partial or complete resolution by viitue of unequal rates of reaction of the enantiomers in a racemate with a chiral catalyst [5]. The method usually forms two products one enantiomer does not react with the chiral catalyst or else it reacts very slowly whilst the other enantiomer reacts with the aid of the chiral catalyst to form a new product which may or may not be chiral. As a result two different compounds now make up the mixture and can be separated by conventional chromatographic techniques. One of the most widely applied examples of this technique is the Sharpless Kinetic Resolution. This asymmetric epoxidation of ally lie alcohols was reported by Sharpless in 1980 catalysed by a titanium (IV) tartrate complex in the presence of a hydroperoxide [6] and has been employed in a number of kinetic resolutions [7]. This reaction shows remarkable... 

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