Olefination Still-Gennari

Fig. 11.15. Analysis of the overall stereoselectivity of a Still—Gennari olefination such as the one in Figure 11.13 simple diastereoselectivity of the formation of the alkoxide intermediate from the achiral phosphonate A and the achiral aldehyde B. For both reagents the terms "back face" and "front face" refer to the selected projection.

Fig. 11.16. Analysis of the simple diastereoselectivity of a Still-Gennari olefination that starts from the enantiomeri-cally pure phosphonate A and the achiral aldehyde B.

Fig. 11.19. Still-Gennari olefination of a racemic a-chi-ral aldehyde with an enan-tiomerically pure phosphonate as kinetic resolution I—Loss of the unreactive enantiomer ent-B of the aldehyde (R stands for the phenylmenthyl group in the Horner-Wadsworth-Emmons products the naming of the products in this figure is in agreement with the nomenclature of Figures 11.17 and 11.18).

A completely analogous kinetic resolution succeeds with the Still-Gennari olefination of Figure 11.20. Here the racemic substrate is a different oc-chiral aldehyde. It carries a sulfon-... 

The Still-Gennari olefination in Figure 11.21 is recommended to anyone who wants to enjoy a third stereochemical dehcacy. The substrate is a dialdehyde that contains oxygenated stereocenters in both a-positions. Nevertheless, this aldehyde is achiral because it has a mirror plane and thus represents a mew-compound. Meso-compounds can sometimes be con-... 

The Still-Gennari olefinations of Figures 9.17-9.22 start from similar substrates as those shown in Figure 9.16. However, at least one of them is chiral. Since each of these... 

We now analyze the Still-Gennari olefination of Figure 9.18. The reagents there are the enantiomerically pure chiral phosphonate A, with which you are familiar from Figure 9.17, and an enantiomerically pure a-chiral aldehyde B. The diastereoselectivity of the formation of the crucial alkoxide intermediate(s) is in this case determined by the interplay of three factors ... 

The mismatched case of a Still-Gennari olefination, which corresponds to the matched case of Figure 9.18, can be found in Figure 9.19. There, reagent control and substrate control act against each other. The substrate in Figure 9.19 is the enantiomer... 

Mulzer (Scheme 8 upper left) obtained the a,/(-unsaturated ester 33 with Z configuration from aldehyde 26a via a Still-Gennari olefination with phosphonate ester 34. Reduction of the ester with DIBAH and application of L-imidazole-PPhj gives allylic iodide 35. This acts as electrophile on the -anion of sulfone 36. After reductive removal of the phenylsulfone, group 28b is obtained [23]. 

Also obtained were significant amounts of allyl alcohol 49 and its trans-isomer 53, resulting from the reduction of the aldehyde 54. The structures were confirmed by comparison with authentic samples that were prepared from the trans Still-Gennari olefin 51. The mechanism of this double bond isomerization is not clear. It occurs at -78 °C even before the aldol reaction takes place and may be the consequence of an addition/elimination process of chloride or triethylamine induced by boron coordination to the aldehyde oxygen atom, but this is speculative. However, I should note at this point that exposing aldehyde 8 separately to all the reagents used in the process produces no change apart from minimal reduction in the presence of (+)-DIP-Cl. 

Scheme 3.20 High stereoselectivity (>98%) observed in the synthesis of (2Z,4 )-ethyl undeca-2,4-dienoic esters. Scope and limitations of the Still—Gennari olefination [104].

In addition to the previously mentioned chirons, albeit with less frequency, a variety of other chiral precursors have been used in the synthesis of natural 5,6-dihydropyrones [3]. Some of them have been prepared with the aid of enzymes. For example, a synthesis of both enantiomers of the natural dihydropyrone rugulactone was based on the enzymatic resolution of the racemic ester 37, obtained in four steps from 1,3-propanediol (Scheme 2.8) [lOh]. Thus, enzymatic hydrolysis of 37 was best catalyzed by a lipase isolated from Candida rugosa and afforded optically enriched (ii)-ester 38 and (S)-alcohol 39. Saponification of 38 was followed by desilylation and selective oxidation of the primary alcohol function to yield aldehyde 40. Still-Gennari olefination of 40 provided Z-a,fl-enoate 41, easily cycUzed to lactone... 

A new, complementary approach to enyne metathesis has also emerged in the work of Singh and Ghosh (Scheme 1.12) [50, 51]. A stepwise methylenation (using dimethyl sulfonium methylide ylide 78) and Stille-Gennari olefination sequence... 

The epothilones A-E, 72-73, have shown their eminent cytotoxic activity against tumor celts, taxol-like mitose inhibition and toxity against multiple drug-resistant tumor cell lines. Ohler and co-workers have developed an easy access to epothilones A-D, in which the intermediate 71 was obtained in 89% yield from aldehyde 69 and only the (Z)-isomer, C12-Ci3, was formed by Still-Gennari olefination condition. ... 

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